Updated on 2022/10/01

写真a

 
TSUJI Takehito
 
Organization
Faculty of Environmental and Life Science Associate Professor
Position
Associate Professor
External link

Degree

  • 学術博士(農学) ( 岡山大学 )

Research Interests

  • Animal genetics

  • 動物遺伝学

Research Areas

  • Life Science / Animal production science

  • Life Science / Applied molecular and cellular biology

  • Life Science / Laboratory animal science

  • Life Science / Animal production science

Education

  • Okayama University    

    - 2001

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  • Okayama University   自然科学研究科  

    - 2001

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    Country: Japan

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  • Okayama University    

    - 1994

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  • Okayama University   農学部   総合農業科

    - 1994

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    Country: Japan

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Research History

  • - 岡山大学 環境生命科学研究科 准教授

    2012

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  • - Associate Professor

    2012

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  • Associate Professor

    2010 - 2012

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  • 岡山大学 自然科学研究科 准教授

    2010 - 2012

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  • - 岡山大学環境生命科学研究科 准教授

    2010

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  • - Associate Professor,Graduate School of Environmental and life Science,Okayama University

    2010

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  • Research Associate

    2002 - 2010

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  • Okayama University   Faculty of Agriculture

    2002 - 2010

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  • Research Associate

    1999 - 2002

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  • Okayama University   Dental School

    1999 - 2002

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Professional Memberships

 

Papers

  • Genetic variants of RNF212 involved in meiotic recombination rate and its relation with conception rate in Japanese Black cattle

    Thu Nu Anh LE, Trung Ba NGUYEN, Ripon Chandra PAUL, Yu OKUDA, Takehito TSUJI, Takayuki IBI, Shinji SASAKI, Tetsuo KUNIEDA

    The Journal of Animal Genetics   49 ( 1 )   13 - 17   2021

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    Publishing type:Research paper (scientific journal)   Publisher:Japanese Society of Animal Breeding and Genetics  

    DOI: 10.5924/abgri.49.13

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  • Genetic characterization of Kushum horses in Kazakhstan based on haplotypes of mtDNA and Y chromosome, and genes associated with important traits of the horses

    Trung B. NGUYEN, Ripon C. PAUL, Yu OKUDA, Thu N. A. LE, Phuong T. K. PHAM, Kushaliye J. KAISSAR, Akhmedenov KAZHMURAT, Sarsenova BIBIGUL, Meirat BAKHTIN, Polat KAZYMBET, Suleimenov Zh MARATBEK, Alikhan MELDEBEKOV, Masahide NISHIBORI, Takayuki IBI, Takehito TSUJI, Tetsuo KUNIEDA

    Journal of Equine Science   31 ( 3 )   35 - 43   2020

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    Publishing type:Research paper (scientific journal)   Publisher:Japan Society of Equine Science  

    DOI: 10.1294/jes.31.35

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  • A mutation in the nuclear pore complex gene Tmem48 causes gametogenesis defects in skeletal fusions with sterility (sks) mice. Reviewed

    Akiyama K, Noguchi J, Hirose M, Kajita S, Katayama K, Khalaj M, Tsuji T, Fairfield H, Byers C, Reinholdt L, Ogura A, Kunieda T

    The Journal of biological chemistry   288 ( 44 )   31830 - 31841   2013.11

  • Screening of TMEM48 binding proteins in testis by yeast two-hybrid method

    KAJITA Shimpei, AKIYAMA Kouyou, TSUJI Takehito, KUNIEDA Tetsuo

    The Journal of animal genetics   41 ( 2 )   77 - 86   2013

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    Language:Japanese   Publisher:Japanese Society of Animal Breeding and Genetics  

    Tmem48 encodes a nuclear membrane protein comprising the nuclear pore complex and a mutation in this gene is responsible for the gametogenesis defects and skeletal malformations in the sks mutant mice. Since a nucleotide substitution in the Tmem48 gene results in arrest of meiosis that causes defective spermatogenesis in the sks mice, the function of nuclear pore complex thorough TMEM48 is suggested to be essential for mammalian gametogenesis. In the present study, therefore, we attempted to identify proteins that have potentially important functions in mammalian gametogenesis by screening of the testis expressing proteins that bind to TMEM48 using yeast two-hybrid method. As a result of the screening, we identified total of 31 proteins which are suggested to interact with TMEM48. The expression analysis of these genes in various mouse tissues indicated specific expressions of Dynll2, Pabpc2, Spink2, Txnl4b genes in the testis. Then, we examined expressions of these genes during the first wave of spermatogenesis at new born stages, in which synchronized spermatogenesis is observed in all seminiferous tubules, and found that these genes express at specific stages of meiosis during spermatogenesis. These findings suggested that the proteins encoded by these genes play essential roles in mammalian gametogenesis.

    DOI: 10.5924/abgri.41.77

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  • Exclusion of NEU1 and PPGB from candidate genes for a lysosomal storage disease in Japanese Black cattle. Reviewed

    Masoudi AA, Yamato O, Yoneda K, Tsuji T, Mikami O, Kunieda T

    Animal science journal = Nihon chikusan Gakkaiho   80 ( 5 )   611 - 615   2009.10

  • Characterization and linkage mapping of an ENU-induced mutant mouse with defective spermatogenesis. Reviewed

    Asano Y, Akiyama K, Tsuji T, Takahashi S, Noguchi J, Kunieda T

    Experimental animals   58 ( 5 )   525 - 532   2009.10

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    Language:English   Publisher:Japanese Association for Laboratory Animal Science  

    repro23 is an autosomal recessive mutation of the mouse generated by the N-ethyl-N-nitrosourea (ENU)-induced mutagenesis program at The Jackson Laboratory. The repro23/repro23 homozygous mouse shows male-specific infertility caused by defective spermatogenesis. In the present study, we investigated the testicular pathology of the affected mouse and performed linkage analysis to determine the chromosomal localization of the repro23 locus. Histological examination of the affected testis showed that the seminiferous epithelium of the repro23/repro23 mice contained spermatogonia and early stage spermatocytes, but no spermatids or spermatozoa. Immunohistochemical staining for Hsc70t, a spermatid specific protein, confirmed the absence of elongating spermatids. These findings indicated interruption of the spermatogenesis during meiosis in the repro23/repro23 mouse. By linkage analysis using 137 affected mice of F2 progeny obtained from crosses between repro23/repro23 female and JF1/Ms (+/+) male mice, the repro23 locus was mapped to 2.2-Mb region of mouse chromosome 7. Although this region contains several potential candidate genes for the repro23 mutation, no gene already identified as a cause of defective speramatogenesis was in this region. Therefore, the gene responsible for the repro23 mutation is suggested to be a novel gene which plays an essential role in mammalian spermatogenesis.<br>

    DOI: 10.1538/expanim.58.525

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    Other Link: https://jlc.jst.go.jp/DN/JALC/00340059676?from=CiNii

  • Characterization of the chromosomal inversion associated with the Koa mutation in the mouse revealed the cause of skeletal abnormalities. Reviewed

    Katayama K, Miyamoto S, Furuno A, Akiyama K, Takahashi S, Suzuki H, Tsuji T, Kunieda T

    BMC genetics   10   60   2009.9

  • Polymerase chain reaction-restriction fragment length polymorphism method for identifying carriers of hemophilia A in Japanese brown cattle Reviewed

    Maryam Khalaj, Abdol Rahim Abbasi, Takehito Tsuji, Yasuo Moritomo, Kenichi Shimojo, Tetsuo Kunieda

    Animal Science Journal   77 ( 1 )   122 - 125   2006.2

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    Hemophilia A is a severe congenital bleeding disorder characterized by subcutaneous hematoma and hemorrhage into muscles resulting from a deficiency of blood coagulation factor VIII. The authors have recently reported two cases of hemophilia A in Japanese Brown cattle and identified a nucleotide substitution in the factor VIII gene, resulting in an amino acid substitution of Leu to His, as a possible cause of the deficiency. In the present study, a simple and effective polymerase chain reaction (PCR)-based diagnostic method was developed to identify carriers of this disorder, using a mismatch primer in combination with restriction enzyme digestion. The PCR reaction amplified a 118 bp fragment, which was not digested by the BspT104I restriction enzyme in affected animals but was digested into two fragments in normal animals. Both digested and undigested fragments were observed in carrier animals. This method was applied to identify the carriers of hemophilia A in a population of Japanese Brown cattle. By screening 155 DNA samples from Japanese Brown cattle, except for the dam of the two probands, no carriers were identified. It was therefore concluded that the probands represent isolated cases of hemophilia A, and that the frequency of the mutant allele in the Japanese Brown cattle population is very low. © 2006 Japanese Society of Animal Science.

    DOI: 10.1111/j.1740-0929.2006.00329.x

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MISC

  • Loss of Function of Evc2 in Dental Mesenchyme Leads to Hypomorphic Enamel

    H. Zhang, H. Takeda, T. Tsuji, N. Kamiya, T. Kunieda, Y. Mochida, Y. Mishina

    JOURNAL OF DENTAL RESEARCH   96 ( 4 )   414 - 422   2017.4

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    Ellis-van Creveld (EvC) syndrome is an autosomal-recessive skeletal dysplasia, characterized by short stature and postaxial polydactyly. A series of dental abnormalities, including hypomorphic enamel formation, has been reported in patients with EvC. Despite previous studies that attempted to uncover the mechanism leading to abnormal tooth development, little is known regarding how hypomorphic enamel is formed in patients with EvC. In the current study, using Evc2/Limbin mutant mice we recently generated, we analyzed enamel formation in the mouse incisor. Consistent with symptoms in human patients, we observed that Evc2 mutant mice had smaller incisors with enamel hypoplasia. Histologic observations coupled with ameloblast marker analyses suggested that Evc2 mutant preameloblasts were capable of differentiating to secretory ameloblasts; this process, however, was apparently delayed, due to delayed odontoblast differentiation, mediated by a limited number of dental mesenchymal stem cells in Evc2 mutant mice. This concept was further supported by the observation that dental mesenchymal-specific deletion of Evc2 phenocopied the tooth abnormalities in Evc2 mutants. Overall, our findings suggest that mutations in Evc2 affect dental mesenchymal stem cell homeostasis, which further leads to hypomorphic enamel formation.

    DOI: 10.1177/0022034516683674

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  • Elevated Fibroblast Growth Factor Signaling Is Critical for the Pathogenesis of the Dwarfism in Evc2/Limbin Mutant Mice

    Honghao Zhang, Nobuhiro Kamiya, Takehito Tsuji, Haruko Takeda, Greg Scott, Sudha Rajderkar, Manas K. Ray, Yoshiyuki Mochida, Benjamin Allen, Veronique Lefebvre, Irene H. Hung, David M. Ornitz, Tetsuo Kunieda, Yuji Mishina

    PLOS GENETICS   12 ( 12 )   2016.12

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    Ellis-van Creveld (EvC) syndrome is a skeletal dysplasia, characterized by short limbs, postaxial polydactyly, and dental abnormalities. EvC syndrome is also categorized as a ciliopathy because of ciliary localization of proteins encoded by the two causative genes, EVC and EVC2 (aka LIMBIN). While recent studies demonstrated important roles for EVC/EVC2 in Hedgehog signaling, there is still little known about the pathophysiological mechanisms underlying the skeletal dysplasia features of EvC patients, and in particular why limb development is affected, but not other aspects of organogenesis that also require Hedgehog signaling. In this report, we comprehensively analyze limb skeletogenesis in Evc2 mutant mice and in cell and tissue cultures derived from these mice. Both in vivo and in vitro data demonstrate elevated Fibroblast Growth Factor (FGF) signaling in Evc2 mutant growth plates, in addition to compromised but not abrogated Hedgehog-PTHrP feedback loop. Elevation of FGF signaling, mainly due to increased Fgf18 expression upon inactivation of Evc2 in the perichondrium, critically contributes to the pathogenesis of limb dwarfism. The limb dwarfism phenotype is partially rescued by inactivation of one allele of Fgf18 in the Evc2 mutant mice. Taken together, our data uncover a novel pathogenic mechanism to understand limb dwarfism in patients with Ellis-van Creveld syndrome.

    DOI: 10.1371/journal.pgen.1006510

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  • Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development

    Mohammed K. Badri, Honghao Zhang, Yoshio Ohyama, Sundharamani Venkitapathi, Nobuhiro Kamiya, Haruko Takeda, Manas Ray, Greg Scott, Takehito Tsuji, Tetsuo Kunieda, Yuji Mishina, Yoshiyuki Mochida

    ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY   299 ( 8 )   1110 - 1120   2016.8

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    Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3-, and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by similar to 20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length, and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. Anat Rec, 299:1110-1120, 2016. (C) 2016 Wiley Periodicals, Inc.

    DOI: 10.1002/ar.23353

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  • Expression of Evc2 in craniofacial tissues and craniofacial bone defects in Evc2 knockout mouse

    Mohammed K. Badri, Honghao Zhang, Yoshio Ohyama, Sundharamani Venkitapathi, Ahmed Alamoudi, Nobuhiro Kamiya, Haruko Takeda, Manas Ray, Greg Scott, Takehito Tsuji, Tetsuo Kunieda, Yuji Mishina, Yoshiyuki Mochida

    ARCHIVES OF ORAL BIOLOGY   68   142 - 152   2016.8

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    Objective: Our objectives were to determine the expression of EVC2 in craniofacial tissues and investigate the effect of Evc2 deficiency on craniofacial bones using Evc2 knockout (KO) mouse model.Design: Evc2 KO mice were generated by introducing a premature stop codon followed by the Internal Ribosomal Entry Site fused to beta-galactosidase (LacZ). Samples from wild-type (WT), heterozygous (Het) and homozygous Evc2 KO mice were prepared. LacZ staining and immunohistochemistry (IHC) with anti-beta-galactosidase, anti-EVC2 and anti-SOX9 antibodies were performed. The craniofacial bones were stained with alcian blue and alizarin red.Results: The LacZ activity in KO was mainly observed in the anterior parts of viscerocranium. The Evc2-expressing cells were identified in many cartilageous regions by IHC with anti-beta-galactosidase antibody in KO and Het embryos. The endogenous EVC2 protein was observed in these areas in WT embryos. Double labeling with anti-SOX9 antibody showed that these cells were mainly chondrocytes. At adult stages, the expression of EVC2 was found in chondrocytes of nasal bones and spheno-occipital synchondrosis, and osteocytes and endothelial-like cells of the premaxilla and mandible. The skeletal double staining demonstrated that craniofacial bones, where the expression of EVC2 was observed, in KO had the morphological defects as compared to WT.Conclusion: To our knowledge, our study was the first to identify the types of Evc2-expressing cells in craniofacial tissues. Consistent with the expression pattern, abnormal craniofacial bone morphology was found in the Evc2 KO mice, suggesting that EVC2 may be important during craniofacial growth and development. (C) 2016 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.archoralbio.2016.05.002

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  • Expression of Evc2 in craniofacial tissues and craniofacial bone defects in Evc2 knockout mouse

    Mohammed K. Badri, Honghao Zhang, Yoshio Ohyama, Sundharamani Venkitapathi, Ahmed Alamoudi, Nobuhiro Kamiya, Haruko Takeda, Manas Ray, Greg Scott, Takehito Tsuji, Tetsuo Kunieda, Yuji Mishina, Yoshiyuki Mochida

    ARCHIVES OF ORAL BIOLOGY   68   142 - 152   2016.8

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    Objective: Our objectives were to determine the expression of EVC2 in craniofacial tissues and investigate the effect of Evc2 deficiency on craniofacial bones using Evc2 knockout (KO) mouse model.Design: Evc2 KO mice were generated by introducing a premature stop codon followed by the Internal Ribosomal Entry Site fused to beta-galactosidase (LacZ). Samples from wild-type (WT), heterozygous (Het) and homozygous Evc2 KO mice were prepared. LacZ staining and immunohistochemistry (IHC) with anti-beta-galactosidase, anti-EVC2 and anti-SOX9 antibodies were performed. The craniofacial bones were stained with alcian blue and alizarin red.Results: The LacZ activity in KO was mainly observed in the anterior parts of viscerocranium. The Evc2-expressing cells were identified in many cartilageous regions by IHC with anti-beta-galactosidase antibody in KO and Het embryos. The endogenous EVC2 protein was observed in these areas in WT embryos. Double labeling with anti-SOX9 antibody showed that these cells were mainly chondrocytes. At adult stages, the expression of EVC2 was found in chondrocytes of nasal bones and spheno-occipital synchondrosis, and osteocytes and endothelial-like cells of the premaxilla and mandible. The skeletal double staining demonstrated that craniofacial bones, where the expression of EVC2 was observed, in KO had the morphological defects as compared to WT.Conclusion: To our knowledge, our study was the first to identify the types of Evc2-expressing cells in craniofacial tissues. Consistent with the expression pattern, abnormal craniofacial bone morphology was found in the Evc2 KO mice, suggesting that EVC2 may be important during craniofacial growth and development. (C) 2016 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.archoralbio.2016.05.002

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  • Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development

    Mohammed K. Badri, Honghao Zhang, Yoshio Ohyama, Sundharamani Venkitapathi, Nobuhiro Kamiya, Haruko Takeda, Manas Ray, Greg Scott, Takehito Tsuji, Tetsuo Kunieda, Yuji Mishina, Yoshiyuki Mochida

    ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY   299 ( 8 )   1110 - 1120   2016.8

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    Language:English   Publisher:WILEY-BLACKWELL  

    Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3-, and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by similar to 20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length, and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. Anat Rec, 299:1110-1120, 2016. (C) 2016 Wiley Periodicals, Inc.

    DOI: 10.1002/ar.23353

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  • Homeobox family Hoxc localization during murine palate formation

    Azumi Hirata, Kentaro Katayama, Takehito Tsuji, Hideto Imura, Nagato Natsume, Toshio Sugahara, Tetsuo Kunieda, Hiroaki Nakamura, Yoshinori Otsuki

    CONGENITAL ANOMALIES   56 ( 4 )   172 - 179   2016.7

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    Homeobox genes play important roles in craniofacial morphogenesis. However, the characteristics of the transcription factor Hoxc during palate formation remain unclear. We examined the immunolocalization patterns of Hoxc5, Hoxc4, and Hoxc6 in palatogenesis of cleft palate (Eh/Eh) mice. On the other hand, mutations in the FGF/FGFR pathway are exclusively associated with syndromic forms of cleft palate. We also examined the immunolocalization of Fgfr1 and Erk1/2 to clarify their relationships with Hoxc in palatogenesis. Some palatal epithelial cells showed Hoxc5 labeling, while almost no labeling of mesenchymal cells was observed in +/+ mice. As palate formation progressed in +/+ mice, Hoxc5, Hoxc4, and Hoxc6 were observed in medial epithelial seam cells. Hoxc5 and Hoxc6 were detected in the oral epithelium. The palatal mesenchyme also showed intense staining for Fgfr1 and Erk1/2 with progression of palate formation. In contrast, the palatal shelves of Eh/Eh mice exhibited impaired horizontal growth and failed to fuse, resulting in a cleft. Hoxc5 was observed in a few epithelial cells and diffusely in the mesenchyme of Eh/Eh palatal shelves. No or little labeling of Fgfr1 and Erk1/2 was detected in the cleft palate of Eh/Eh mice. These findings suggest that Hoxc genes are involved in palatogenesis. Furthermore, there may be the differences in the localization pattern between Hoxc5, Hoxc4, and Hoxc6. Additionally, Hoxc distribution in palatal cells during palate development may be correlated with FGF signaling. (228/250 words) (c) 2016 Japanese Teratology Society

    DOI: 10.1111/cga.12153

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  • Homeobox family Hoxc localization during murine palate formation

    Azumi Hirata, Kentaro Katayama, Takehito Tsuji, Hideto Imura, Nagato Natsume, Toshio Sugahara, Tetsuo Kunieda, Hiroaki Nakamura, Yoshinori Otsuki

    CONGENITAL ANOMALIES   56 ( 4 )   172 - 179   2016.7

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    Homeobox genes play important roles in craniofacial morphogenesis. However, the characteristics of the transcription factor Hoxc during palate formation remain unclear. We examined the immunolocalization patterns of Hoxc5, Hoxc4, and Hoxc6 in palatogenesis of cleft palate (Eh/Eh) mice. On the other hand, mutations in the FGF/FGFR pathway are exclusively associated with syndromic forms of cleft palate. We also examined the immunolocalization of Fgfr1 and Erk1/2 to clarify their relationships with Hoxc in palatogenesis. Some palatal epithelial cells showed Hoxc5 labeling, while almost no labeling of mesenchymal cells was observed in +/+ mice. As palate formation progressed in +/+ mice, Hoxc5, Hoxc4, and Hoxc6 were observed in medial epithelial seam cells. Hoxc5 and Hoxc6 were detected in the oral epithelium. The palatal mesenchyme also showed intense staining for Fgfr1 and Erk1/2 with progression of palate formation. In contrast, the palatal shelves of Eh/Eh mice exhibited impaired horizontal growth and failed to fuse, resulting in a cleft. Hoxc5 was observed in a few epithelial cells and diffusely in the mesenchyme of Eh/Eh palatal shelves. No or little labeling of Fgfr1 and Erk1/2 was detected in the cleft palate of Eh/Eh mice. These findings suggest that Hoxc genes are involved in palatogenesis. Furthermore, there may be the differences in the localization pattern between Hoxc5, Hoxc4, and Hoxc6. Additionally, Hoxc distribution in palatal cells during palate development may be correlated with FGF signaling. (228/250 words) (c) 2016 Japanese Teratology Society

    DOI: 10.1111/cga.12153

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  • Genetic characterization of a rare line of Japanese Black cattle in Okayama prefecture

    YONEDA Kazuhiro, OKUDA Yu, Siqintuya, NISHIMAKI Takahiro, MATSUMOTO Hirokazu, MIYAZAKI Yoshiyuki, IBI Takayuki, TSUJI Takehito, KUNIEDA Tetsuo

    Nihon Chikusan Gakkaiho   87 ( 1 )   1 - 10   2016

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    The effective population size of Japanese Black cattle has been significantly reduced and maintaining the genetic diversity of the population is important for breeding of Japanese Black cattle. For the conservation of genetic diversity, use of different lines of the breed with unique genetic characteristics for breeding, instead of intensive use of sires of few particular lines as common in current breeding of Japanese Black cattle, will be effective to prevent the genetic homogenization of the population. In the present study, we performed genetic characterization a population of a rare line of Japanese Black cattle, which has been originated from ancestral &quot;Tsuru-ushi&quot; in Okayama prefecture. By using microsatellite markers, allelic richness, and average observed and expected heterozygosity are 3.48, 0.514, and 0.511, respectively, and these values were lower than those of most of the Japanese Black cattle local subpopulations compared. The result of the clustering analyses indicated that the animals of the rare line formed a single group with a cluster that was clearly distinguished from the other populations. Sequence analysis of mitochondrial D-loop region revealed that only two haplotypes were observed in the population and 80% of the animals in the population possess a single haplotype. However, the other haplotype was a novel unique haplotype that has not been reported in cattle. Genotyping of six genes associated with important traits revealed that &lt;i&gt;SREBP1&lt;/i&gt; and &lt;i&gt;NCAPG&lt;/i&gt; loci were fixed for a single allele in the population and more than 90% of animals possess an allele of &lt;i&gt;MC1R&lt;/i&gt; locus. These findings indicated that while genetic diversity of the population of the rare line is lower than those of the Japanese Black cattle local subpopulations, this population has unique genetic characteristics that were distinguished from the other populations and, therefore, the rare line is important for maintaining genetic diversity of Japanese Black cattle.

    DOI: 10.2508/chikusan.87.1

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  • Generation of Evc2/Limbin Global and Conditional KO Mice and Its Roles during Mineralized Tissue Formation

    Honghao Zhang, Haruko Takeda, Takehito Tsuji, Nobuhiro Kamiya, Sudha Rajderkar, Ke'Ale Louie, Crystal Collier, Greg Scott, Manas Ray, Yoshiyuki Mochida, Vesa Kaartinen, Tetsuo Kunieda, Yuji Mishina

    GENESIS   53 ( 9 )   612 - 626   2015.9

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    Ellis-van Creveld (EvC) syndrome (OMIM 225500) is an autosomal recessive disease characterized with chondrodysplastic dwarfism in association with abnormalities in oral cavity. Ciliary proteins EVC and EVC2 have been identified as causative genes and they play an important role on Hedgehog signal transduction. We have also identified a causative gene LIMBIN for bovine chondrodysplastic dwarfism (bcd) that is later identified as the bovine ortholog of EVC2. Here, we report generation of conventional and conditional mutant Evc2/Limbin alleles that mimics mutations found in EvC patients and bcd cattle. Resulted homozygous mice showed no ciliary localization of EVC2 and EVC and displayed reduced Hedgehog signaling activity in association with skeletal and oral defects similar to the EvC patients. Cartilage-specific disruption of Evc2/Limbin resulted in similar but milder skeletal defects, whereas osteoblast-specific disruption did not cause overt changes in skeletal system. Neural crest-specific disruption of Evc2/Limbin resulted in defective incisor growth similar to that seen in conventional knockouts; however, differentiation of amelobolasts was relatively normal in the conditional knockouts. These results showcased functions of EVC2/LIMBIN during formation of mineralized tissues. Availability of the conditional allele for this gene should facilitate further detailed analyses of the role of EVC2/LIMBIN in pathogenesis of EvC syndrome. (C) 2015 Wiley Periodicals, Inc.

    DOI: 10.1002/dvg.22879

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  • Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle

    Akiko Takasuga, Kunio Sato, Ryouichi Nakamura, Yosuke Saito, Shinji Sasaki, Takehito Tsuji, Akio Suzuki, Hiroshi Kobayashi, Tamako Matsuhashi, Koji Setoguchi, Hiroshi Okabe, Toshitake Ootsubo, Ichiro Tabuchi, Tatsuo Fujita, Naoto Watanabe, Takashi Hirano, Shota Nishimura, Toshio Watanabe, Makio Hayakawa, Yoshikazu Sugimoto, Takatoshi Kojima

    PLOS GENETICS   11 ( 8 )   e1005433   2015.8

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    Recessive skeletal dysplasia, characterized by joint- and/or hip bone-enlargement, was mapped within the critical region for a major quantitative trait locus (QTL) influencing carcass weight; previously named CW-3 in Japanese Black cattle. The risk allele was on the same chromosome as the Q allele that increases carcass weight. Phenotypic characterization revealed that the risk allele causes disproportional tall stature and bone size that increases carcass weight in heterozygous individuals but causes disproportionately narrow chest width in homozygotes. A non-synonymous variant of FGD3 was identified as a positional candidate quantitative trait nucleotide (QTN) and the corresponding mutant protein showed reduced activity as a guanine nucleotide exchange factor for Cdc42. FGD3 is expressed in the growth plate cartilage of femurs from bovine and mouse. Thus, loss of FDG3 activity may lead to subsequent loss of Cdc42 function. This would be consistent with the columnar disorganization of proliferating chondrocytes in chondrocyte-specific inactivated Cdc42 mutant mice. This is the first report showing association of FGD3 with skeletal dysplasia.

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  • 岡山県のジャージー集団におけるBCO2遺伝子の新たな変異と脂肪淡黄色との関連性

    清水佑起, 石倉健一, 揖斐隆之, 国枝哲夫, 辻岳人

    日本畜産学会大会講演要旨   119th   115   2015.3

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  • 骨格異常と枝肉重量QTL(CW‐3)は体高の増加と胸幅の減少によって説明される

    高須賀晶子, 齊藤陽介, 佐藤邦雄, 中村亮一, 小林宙, 松橋珠子, 鈴木晶夫, 瀬戸口浩二, 佐々木慎二, 早川磨紀男, 辻岳人, 小島孝敏

    日本畜産学会大会講演要旨   119th   171 - 171   2015.3

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  • 精子頭部及び尾部の形成異常を呈するENU誘発ミュータントマウス(repro20,21)の原因遺伝子の同定

    松本大和, 奥田ゆう, 藤原靖浩, 秋山耕陽, 辻岳人, 国枝哲夫

    J Reprod Dev   60 ( Suppl Japanese Issue )   J63 - j63   2014.8

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  • Role of Ellis-van Creveld syndrome2 (Evc2) in craniofacial development

    Mohammed K. Badri, Honghao Zhang, Nobuhiro Kamiya, Takehito Tsuji, Tetsuo Kunieda, Yuji Mishina, Yoshiyuki Mochida

    AMERICAN JOURNAL OF MEDICAL GENETICS PART A   164 ( 8 )   1876 - 1877   2014.8

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  • 不妊を呈するENU誘発ミュータントマウス(repro57)雌の表現型解析

    筑紫未津穂, 藤原靖浩, 松本大和, 秋山耕陽, 辻岳人, 国枝哲夫

    日本実験動物学会総会講演要旨集   61st   261   2014.5

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  • Characterization of the Skeletal Fusion with Sterility (sks) Mouse Showing Axial Skeleton Abnormalities Caused by Defects of Embryonic Skeletal Development

    Kouyou Akiyama, Kentaro Katayama, Takehito Tsuji, Tetsuo Kunieda

    EXPERIMENTAL ANIMALS   63 ( 1 )   11 - 19   2014.1

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    The development of the axial skeleton is a complex process, consisting of segmentation and differentiation of somites and ossification of the vertebrae. The autosomal recessive skeletal fusion with sterility (sks) mutation of the mouse causes skeletal malformations due to fusion of the vertebrae and ribs, but the underlying defects of vertebral formation during embryonic development have not yet been elucidated. For the present study, we examined the skeletal phenotypes of sks/sks mice during embryonic development and the chromosomal localization of the sks locus. Multiple defects of the axial skeleton, including fusion of vertebrae and fusion and bifurcation of ribs, were observed in adult and neonatal sks/sks mice. In addition, we also found polydactyly and delayed skull ossification in the sks/sks mice. Morphological defects, including disorganized vertebral arches and fusions and bifurcations of the axial skeletal elements, were observed during embryonic development at embryonic day 12.5 (E12.5) and E14.5. However, no morphological abnormality was observed at E11.5, indicating that defects of the axial skeleton are caused by malformation of the cartilaginous vertebra and ribs at an early developmental stage after formation and segmentation of the somites. By linkage analysis, the sks locus was mapped to an 8-Mb region of chromosome 4 between D4Mit331 and D4Mit199. Since no gene has already been identified as a cause of malformation of the vertebra and ribs in this region, the gene responsible for sks is suggested to be a novel gene essential for the cartilaginous vertebra and ribs.

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  • 口之島牛集団における経済形質、遺伝性疾患および毛色に関連する遺伝子の対立遺伝子頻度とその分布

    動物遺伝育種研究   42 ( 1 )   11 - 19   2014

  • Phenotypic Characterization of Ggt1dwg/dwg Mice, a Mouse Model for Hereditary gamma-Glutamyl Transferase Deficiency

    Kaoru Yamada, Takehito Tsuji, Tetsuo Kunieda

    EXPERIMENTAL ANIMALS   62 ( 2 )   151 - 157   2013.4

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    Ggt1(dwg/dwg) mice are spontaneous mutant mice with a nucleotide deletion in the Ggt1 gene. They are characterized by dwarfism, cataract, and coat color abnormality. These abnormalities in the external appearance of Ggt1(dwg/dwg) mice closely resemble those of previously reported GGT1-deficient mice, Ggt1(tm1Zuk/tm1Zuk) (Ggt1(-/-)) and Ggt1(enu1/enu1), generated by gene targeting or ENU mutagenesis. However, whether the pathological features of Ggt1(dwg/dwg) mice are also similar to those of the Ggt1(-/-) and Ggt1(enu1/enu1) mice remains unclear. To clarify the pathogenesis of Ggt1(dwg/dwg) mice, we physiologically and histologically investigated the abnormalities of Ggt1(dwg/dwg) mice in this study. First, we analyzed the activity of GGT1 and GSH levels in Ggt1(dwg/dwg) mice. GGT1 activity in the Ggt1(dwg/dwg) mice was reduced to approximately 4.0% of that in the wild-type mice. Plasma and kidney GSH levels were markedly increased, while eye and liver GSH levels were markedly decreased, in the Ggt1(dwg/dwg) mice. Notably, no significant difference in survival rate was observed between the Ggt1(dwg/dwg) and wild-type mice, whereas high mortality was reported in the Ggt1(-/-) and Ggt1(enu1/enu1) mice. Growth retardation, degeneration of lens fibers, and an increased number of osteoclasts in the Ggt1(dwg/dwg) mice were reversed by administration of N-acetyl-L-cysteine, a precursor of GSH synthesis. Thus, we conclude that the abnormalities of Ggt1(dwg/dwg) mice are caused by alteration of the GSH levels due to the depression of GGT1 activity and that Ggt1(dwg/dwg) mice will be a useful model for GGT deficiency with peculiar features.

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  • Heparanase Localization during Palatogenesis in Mice

    Azumi Hirata, Kentaro Katayama, Takehito Tsuji, Nagato Natsume, Toshio Sugahara, Yuichi Koga, Kazufumi Takano, Yoshinori Otsuki, Hiroaki Nakamura

    BIOMED RESEARCH INTERNATIONAL   2013

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    Palatogenesis is directed by epithelial-mesenchymal interactions and results partly from remodeling of the extracellular matrix (ECM) of the palatal shelves. Here, we assessed heparanase distribution in developing mouse palates. No heparanase was observed in the vertically oriented palatal shelves in early stages of palate formation. As palate formation progressed, the palatal shelves were reorganized and arranged horizontally above the tongue, and heparanase localized to the epithelial cells of these shelves. When the palatal bilateral shelves first made contact, the heparanase localized to epithelial cells at the tips of shelves. Later in fusing palatal shelves, the cells of the medial epithelial seam (MES) were labeled with intense heparanase signal. In contrast, the basement membrane heparan sulfate (HS) was scarcely observed in the palatal shelves in contact. Moreover, perlecan labeling was sparse in the basement membrane of the MES, on which laminin and type IV collagen were observed. Moreover, we assessed the distribution of matrix metalloproteinase- (MMP-) 9, MMP-2, and MMP-3 in developing mouse palates and these MMPs were observed in the MES. Our findings indicated that heparanase was important for palate formation because it mediated degradation of the ECM of palatal shelves. Heparanase may, in concert with other proteases, participate in the regression of the MES.

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  • CNP/NPR2 signaling maintains oocyte meiotic arrest in early antral follicles and is suppressed by EGFR-mediated signaling in preovulatory follicles

    Takehito Tsuji, Chiyo Kiyosu, Kouyou Akiyama, Tetsuo Kunieda

    MOLECULAR REPRODUCTION AND DEVELOPMENT   79 ( 11 )   795 - 802   2012.11

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    Oocyte meiosis is arrested at prophase I by factors secreted from surrounding somatic cells after oocytes acquire meiotic competence at an early antral stage, and meiosis resumes in preovulatory follicles as a result of the luteinizing hormone (LH) surge. Recently, signaling by C-type natriuretic peptide (CNP) through its receptor, natriuretic peptide receptor 2 (NPR2), was found to be essential for meiotic arrest at the late antral stage. Whether or not CNP/NPR2 signaling maintains oocyte meiotic arrest in earlier follicular stages and how it is associated with meiotic resumption induced by the LH surge is unclear. In this study, we examined the expression of Nppc and Npr2, respectively encoding CNP and NPR2, in the ovaries of immature mice. Nppc and Npr2 mRNA were specifically expressed in the outer and inner granulosa cell layers, respectively, in early antral follicles. Histological analysis of mice with a mutation in Npr2 revealed precocious resumption of oocyte meiosis in early antral follicles. Ovaries of mice treated with excess human chorionic gonadotropin (hCG) exhibited markedly decreased Nppc mRNA levels in granulosa cells of preovulatory follicles. Moreover, we found that amphiregulin, a mediator of LH/hCG activity through epidermal growth factor receptor (EGFR), suppressed Nppc mRNA levels in cultured granulosa cells. These results suggest that CNP/NPR2 signaling is essential for oocyte meiotic arrest in early antral follicles and that activated LH/amphiregulin/EGFR signaling pathway suppresses this signal by downregulating Nppc expression. Mol. Reprod. Dev. 79: 795802, 2012. (C) 2012 Wiley Periodicals, Inc.

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  • NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary

    Chiyo Kiyosu, Takehito Tsuji, Kaoru Yamada, Shimpei Kajita, Tetsuo Kunieda

    REPRODUCTION   144 ( 2 )   187 - 193   2012.8

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    Natriuretic peptide type C (NPPC) and its high affinity receptor, natriuretic peptide receptor 2 (NPR2), have been assumed to be involved in female reproduction and have recently been shown to play an essential role in maintaining meiotic arrest of oocytes. However, the overall role of NPPC/NPR2 signaling in female reproduction and ovarian function is still less clear. Here we report the defects observed in oocytes and follicles of mice homozygous for Nppc(lbab) or Npr2(cn), mutant alleles of Nppc or Npr2 respectively to clarify the exact consequences of lack of NPPC/NPR2 signaling in female reproductive systems. We found that: i) Npr2(cn)/Npr2(cn) female mice ovulated a comparable number of oocytes as normal mice but never produced a litter; ii) all ovulated oocytes of Npr2(cn)/Npr2(cn) and Nppc(lbab)/Nppc(lbab) mice exhibited abnormalities, such as fragmented or degenerated ooplasm and never developed to the two-cell stage after fertilization; iii) histological examination of the ovaries of Npr2(cn)/Npr2(cn) and Nppc(lbab)/Nppc(lbab) mice showed that oocytes in antral follicles prematurely resumed meiosis and that immediately before ovulation, oocytes showed disorganized chromosomes or fragmented ooplasm; and iv) ovulated oocytes and oocytes in the periovulatory follicles of the mutant mice were devoid of cumulus cells. These findings demonstrate that NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation, which affects female fertility through the production of oocytes with developmental capacity. Reproduction (2012) 144 187-193

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  • NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary

    Chiyo Kiyosu, Takehito Tsuji, Kaoru Yamada, Shimpei Kajita, Tetsuo Kunieda

    REPRODUCTION   144 ( 2 )   187 - 193   2012.8

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    Natriuretic peptide type C (NPPC) and its high affinity receptor, natriuretic peptide receptor 2 (NPR2), have been assumed to be involved in female reproduction and have recently been shown to play an essential role in maintaining meiotic arrest of oocytes. However, the overall role of NPPC/NPR2 signaling in female reproduction and ovarian function is still less clear. Here we report the defects observed in oocytes and follicles of mice homozygous for Nppc(lbab) or Npr2(cn), mutant alleles of Nppc or Npr2 respectively to clarify the exact consequences of lack of NPPC/NPR2 signaling in female reproductive systems. We found that: i) Npr2(cn)/Npr2(cn) female mice ovulated a comparable number of oocytes as normal mice but never produced a litter; ii) all ovulated oocytes of Npr2(cn)/Npr2(cn) and Nppc(lbab)/Nppc(lbab) mice exhibited abnormalities, such as fragmented or degenerated ooplasm and never developed to the two-cell stage after fertilization; iii) histological examination of the ovaries of Npr2(cn)/Npr2(cn) and Nppc(lbab)/Nppc(lbab) mice showed that oocytes in antral follicles prematurely resumed meiosis and that immediately before ovulation, oocytes showed disorganized chromosomes or fragmented ooplasm; and iv) ovulated oocytes and oocytes in the periovulatory follicles of the mutant mice were devoid of cumulus cells. These findings demonstrate that NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation, which affects female fertility through the production of oocytes with developmental capacity. Reproduction (2012) 144 187-193

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  • Skeletal Analysis of the Long Bone Abnormality (lbab/lbab) Mouse, A Novel Chondrodysplastic C-Type Natriuretic Peptide Mutant

    Eri Kondo, Akihiro Yasoda, Takehito Tsuji, Toshihito Fujii, Masako Miura, Naotestu Kanamoto, Naohisa Tamura, Hiroshi Arai, Tetsuo Kunieda, Kazuwa Nakao

    CALCIFIED TISSUE INTERNATIONAL   90 ( 4 )   307 - 318   2012.4

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    Long bone abnormality (lbab/lbab) is a strain of dwarf mice. Recent studies revealed that the phenotype is caused by a spontaneous mutation in the Nppc gene, which encodes mouse C-type natriuretic peptide (CNP). In this study, we analyzed the chondrodysplastic skeletal phenotype of lbab/lbab mice. At birth, lbab/lbab mice are only slightly shorter than their wild-type littermates. Nevertheless, lbab/lbab mice do not undergo a growth spurt, and their final body and bone lengths are only similar to 60% of those of wild-type mice. Histological analysis revealed that the growth plate in lbab/lbab mice, especially the hypertrophic chondrocyte layer, was significantly thinner than in wild-type mice. Overexpression of CNP in the cartilage of lbab/lbab mice restored their thinned growth plate, followed by the complete rescue of their impaired endochondral bone growth. Furthermore, the bone volume in lbab/lbab mouse was severely decreased and was recovered by CNP overexpression. On the other hand, the thickness of the growth plate of lbab/+ mice was not different from that of wild-type mice; accordingly, impaired endochondral bone growth was not observed in lbab/+ mice. In organ culture experiments, tibial explants from fetal lbab/lbab mice were significantly shorter than those from lbab/+ mice and elongated by addition of 10(-7) M CNP to the same extent as lbab/+ tibiae treated with the same dose of CNP. These results demonstrate that lbab/lbab is a novel mouse model of chondrodysplasia caused by insufficient CNP action on endochondral ossification.

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  • A missense mutation of the Dhh gene is associated with male pseudohermaphroditic rats showing impaired Leydig cell development

    Yasuhiro Kawai, Junko Noguchi, Kouyou Akiyama, Yuriko Takeno, Yasuhiro Fujiwara, Shimpei Kajita, Takehito Tsuji, Kazuhiro Kikuchi, Hiroyuki Kaneko, Tetsuo Kunieda

    REPRODUCTION   141 ( 2 )   217 - 225   2011.2

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    Development of the male gonads is a complex process with interaction of various cells in the gonads including germ, Sertoli, Leydig, and myoid cells. TF is a mutant rat strain showing male pseudohermaphroditism, with agenesis of Leydig cells and androgen deficiency controlled by an autosomal single recessive gene (mp). The mp locus was mapped on the distal region of rat chromosome 7 by linkage analysis, but the gene responsible for the mp mutation has not been identified. In this study, we performed fine linkage mapping and sequence analysis to determine the causative gene of the mp mutation, and performed an immunohistochemical study using a Leydig cell-specific marker to investigate detailed phenotypes of the mutant rats during the testicular development. As a result, we found a missense mutation of the gene encoding Desert hedgehog (Dhh) in the mutant rat, which could result in loss of function of the DHH signaling pathway. Histochemical examination revealed remarkably reduced number of fetal Leydig cells and lack of typical spindle-shaped adult Leydig cell in the mp/mp rats. These phenotypes resembled those of the Dhh-null mice. Additionally, testosterone levels were significantly lower in the mp/mp fetus, indicating androgen deficiency during embryonic development. These results indicate that the mutation of the Dhh gene may be responsible for the pseudohermaphrodite phenotypes of the mutant rat, and that the Dhh gene is probably essential for the development of Leydig cells. Reproduction (2011) 141 217-225

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  • Gastrointestinal Tract Disorder in Natriuretic Peptide Receptor B Gene Mutant Mice

    Chizuru Sogawa, Asaki Abe, Takehito Tsuji, Mitsuru Koizumi, Tsuneo Saga, Tetsuo Kunieda

    AMERICAN JOURNAL OF PATHOLOGY   177 ( 2 )   822 - 828   2010.8

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    Natriuretic peptide receptor B (NPR-B), which has high affinity for C-type natriuretic peptide (CNP) and synthesizes intracellular cGMP, may be involved in gastrointestinal tract (GIT) regulation. A mutant allele of the NPR-B-encoding gene (Npr2) is responsible for the phenotype of the short-limb dwarfism (SLW) mouse. Homozygosity for this autosomal-recessive gene (slw/slw) leads to dwarfism and death before weaning because of milk retention in the stomach and intestinal distention. To elucidate the relationship between CNP/NPR-B signaling and GIT function, we investigated the association between Npr2 mutation and the GIT phenotype in slw/slw mice. The pylorus and large intestine of the mutants did not respond to CNP stimulation; further, they showed pyloric lumen narrowing with randomly aligned circular muscle cells. Comparison of the cGMP and neuronal marker distribution in GIT tissues confirmed cGMP expression in neuronal tissues. An Auerbach&apos;s plexus and submucosal tissues of the mutants didn&apos;t express cGMP and expressed Ca(2+). In contrast, those of normal mice (controls) expressed both cGMP and Ca(2+). Sequencing revealed that the causative Npr2 mutation was a 7-base deletion in exon 8, resulting in a frameshift and premature termination codon appearance. Therefore, the GIT phenotype of slw/slw mice is because of a CNP/NPR-B-signaling defect caused by an Npr2 mutation. These results facilitate better understanding of the role of CNP/NPR-B signaling in GIT motility. (Am J Pathol 2010, 177:822-828; DOI: 10.2353/ajpath.2010.091278)

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  • The Roles of Syntaxin2/Epimorphin (Stx2/Epim) in Progression of Meiosis During Spermatogenesis

    Yasuhiro Fujiwara, Kouyou Akiyama, Yuka Asano, Takehito Tsuji, Junko Noguchi, Tetsuo Kunieda

    BIOLOGY OF REPRODUCTION   136 - 136   2010

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  • Cloning of Candidate Genes for TMEM48 Binding Proteins, Which Could Be Involved in Gametogenesis

    Shimpei Kajita, Kouyou Akiyama, Michiko Hirose, Narumi Ogonuki, Atsuo Ogura, Takehito Tsuji, Tetsuo Kunieda

    BIOLOGY OF REPRODUCTION   136 - 136   2010

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  • Characterization of the dwg mutations: dwg and dwg (Bayer) are new mutant alleles of the Ggt1 gene

    Takehito Tsuji, Kaoru Yamada, Tetsuo Kunieda

    MAMMALIAN GENOME   20 ( 11-12 )   711 - 719   2009.12

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    The dwg and dwg (Bayer) are allelic mutations of the mouse that are characterized by dwarfism, cataracts, and coat color change in homozygotes. The Ggt1 gene encodes gamma-glutamyltransferase 1 (GGT1), an extracellular membrane-bound enzyme that is critical for glutathione homeostasis. Both the dwg locus and Ggt1 gene are localized on mouse chromosome 10, and the phenotypes of GGT1-deficient mice with targeted disruption of the Ggt1 gene show remarkable similarities with those of dwg/dwg and dwg (Bayer) /dwg (Bayer) mice. This evidence led us to hypothesize that the Ggt1 gene is responsible for dwg and dwg (Bayer) mutations. In this study we characterized dwg mutations by investigating their association with the Ggt1 gene. Histological analysis revealed reduced numbers of proliferative and hypertrophic chondrocytes in the growth plate of dwg/dwg mice, which are characteristic abnormalities observed in GGT1-deficient mice. To identify the causative mutations of dwg mutations, we analyzed the Ggt1 gene in dwg/dwg and dwg (Bayer) /dwg (Bayer) mice. In dwg/dwg mice, 13 nucleotides on exon 7 of the Ggt1 gene were deleted, resulting in the generation of aberrant transcripts due to disrupted pre-mRNA splicing. Furthermore, dwg (Bayer) /dwg (Bayer) mice had a 46.7-kb deletion containing complete coding sequences of Ggt1 and AI646023 genes and the first exon of the Ggt5 gene, which is closely related to the Ggt1 gene as a member of the GGT gene family. These results indicate that both dwg and dwg (Bayer) have defective mutations of the Ggt1 gene. Thus, we concluded that mutations in the Ggt1 gene are responsible for the phenotypes of dwg/dwg and dwg (Bayer) /dwg (Bayer) mice.

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  • A mutation of the WFDC1 gene is responsible for multiple ocular defects in cattle

    Abdol Rahim Abbasi, Maryam Khalaj, Takehito Tsuji, Muki Tanahara, Kazuyuki Uchida, Yoshikazu Sugimoto, Tetsuo Kunieda

    GENOMICS   94 ( 1 )   55 - 62   2009.7

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    Multiple ocular defects (MOD) in cattle is an autosomal recessive hereditary disorder characterized by dysplasia of the lens, retinal detachment, persistence of the hyaloid artery, and microphthahmia, The locus responsible for MOD has been mapped to the proximal region of bovine chromosome 18. In the present Study, we refined the localization of the MOD locus to a 1.0-Mb interval by haplotype analysis using a pedigree of affected animals. Comparison of nucleotide sequence of genes in this region revealed a one-nucleotide insertion in the WFDC1 gene, which resulted in a frame shift mutation and premature termination codon at the middle of the protein. WFDC1 is a small secretory protein containing a WAP-type four disulfide core domain. Specific expression of Wfdc1 was observed in the lens, retina, and optic nerves of embryonic and adult mouse eyes by immunohitochemical staining and in situ hybridization. The present finding demonstrated the essential role of WFDC1 in mammalian eye development. (C) 2009 Elsevier Inc. All rights reserved.

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  • Hypomorphic mutation in mouse Nppc gene causes retarded bone growth due to impaired endochondral ossification

    Takehito Tsuji, Eri Kondo, Akihiro Yasoda, Masataka Inamoto, Chiyo Kiyosu, Kazuwa Nakao, Tetsuo Kunieda

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   376 ( 1 )   186 - 190   2008.11

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    Long bone abnormality (lbab/lbab) is a spontaneous mutant mouse characterized by dwarfism with shorter long bones. A missense mutation was reported in the Nppc gene, which encodes C-type natriuretic peptide (CNP), but it has not been confirmed whether this mutation is responsible for the dwarf phenotype. To verify that the mutation causes the dwarfism of lbab/lbab mice, we first investigated the effect of CNP in lbab/lbab mice. By transgenic rescue with chondrocyte-specific expression of CNP, the dwarf phenotype in lbab/lbab mice was completely compensated. Next, we revealed that CNP derived from the lbab allele retained only slight activity to induce cGMP production through its receptor. Histological analysis showed that both proliferative and hypertrophic zones of chondrocytes in the growth plate of lbab/lbab mice were markedly reduced. Our results demonstrate that lbab/lbab mice have a hypomorphic mutation in the Nppc gene that is responsible for dwarfism caused by impaired endochondral ossification. (C) 2008 Elsevier Inc. All rights reserved.

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  • Leydig cell hyperplasia in an ENU-induced mutant mouse with germ cell depletion

    Maryarn Khalaj, Abdol Rahim Abbasi, Ryo Nishimura, Kouyou Akiyama, Takehito Tsuji, Junko Noguchi, Kiyoshi Okuda, Tetsuo Kunieda

    JOURNAL OF REPRODUCTION AND DEVELOPMENT   54 ( 3 )   225 - 228   2008.6

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    Repro22 is an N-ethyl-N-nitrosourea (ENU)-induced mutation in mice showing depletion of both male and. female germ cells. In the present study, we investigated the male phenotypes of the mutant mouse at the adult stage. The repro22/repro22 homozygous mice showed reduced body weights as well as markedly reduced testis weights. Histological examination of the testes at 4 and 10 months of age showed no germ cells in the seminiferous tubules of the affected testis while a number of Sertoli cells were observed in the tubules. In addition to the germ cell depletion, the testes of the affected mouse contained expanded intertubular spaces that were filled by Leydig cell-like interstitial cells. These interstitial cells were confirmed to be Leydig cells by immunohistochmical staining using anti-3 beta-HSD antibody. The estimated number of Leydig cells in the affected testes at 10 months of age increased approximately 2 fold compared with those of normal testes. Furthermore, the plasma testosterone levels of the affected mice at 10 months of age were significantly higher than those of the normal mice. These findings indicated that the repro22/repro22 mouse developed hyperplasia of Leydig cells that was presumably caused by the absence of germ cells in the seminiferous tubules.

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  • A new ENU-induced mutant mouse with defective spermatogenesis caused by a nonsense mutation of the syntaxin 2/Epimorphin (Stx2/Epim) gene

    Kouyou Akiyama, Shiho Akimaru, Yuka Asano, Maryam Khalaj, Chiyo Kiyosu, Ali Akbar Masoudi, Sakino Takahashi, Kentaro Katayama, Takehito Tsuji, Junko Noguchi, Tetsuo Kunieda

    JOURNAL OF REPRODUCTION AND DEVELOPMENT   54 ( 2 )   122 - 128   2008.4

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    Repro34 is an N-ethyl-N-nitrosourea (ENU)-induced mutation in mice showing male-specific infertility caused by defective spermatogenesis. In the present study, we investigated pathogenesis and molecular lesions in relation to spermatogenesis in the repro34/repro34 homozygous mouse. Histological examination of the testis showed that the seminiferous epithelium of the repro34/repro34 mouse contained spermatogonia and spermatocytes but no round and elongating spermatids. Instead of these haploid cells, multinucleated giant cells occupied the niche of the seminiferous tubules. Immunohistochemical staining for Hsc70t, an elongating spermatid specific protein, confirmed the absence of elongating spermatids. Furthermore, RT-PCR showed that there were significantly reduced expressions of the marker genes specifically expressed in the spermatid and that there was no difference in the expressions of the spermatocyte specific marker genes. These findings indicated interruption of the spermatogenesis during transition from the spermatocyte to spermatid in the repro34/repro34 mouse. The repro34 locus has been mapped on a 7.0-Mb region of mouse chromosome 5 containing the Syntaxin 2/Epimorphin (Stx2/Epim) gene, and targeted disruption of this gene has been reported to cause defective spermatogenesis. We therefore sequenced the entire coding region of the Stx2/Epim gene and found a nucleotide substitution that results in a nonsense mutation of this gene. The expression pattern of the Stx2/Epim gene during the first wave of spermatogenesis, increased expression at later stages of spermatogenesis, was in agreement with the affected phase of spermatogenesis in the adult repro34/repro34 testis. We therefore concluded that the male infertility of the repro34/repro34 mouse is caused by the interruption of spermatogenesis during transition from the spermatocyte to spermatid and that the nonsense mutation of the Stx2/Epim gene is responsible for the interruption of spermatogenesis.

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  • Linkage mapping of the locus responsible for forelimb-girdle muscular anomaly of Japanese black cattle on bovine chromosome 26

    A. A. Masoudi, K. Uchida, K. Yokouchi, K. Ohwada, A. R. Abbasi, T. Tsuji, T. Watanabe, T. Hirano, Y. Sugimoto, T. Kunieda

    ANIMAL GENETICS   39 ( 1 )   46 - 50   2008.2

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    Forelimb-girdle muscular anomaly is an autosomal recessive disorder of Japanese black cattle characterized by tremor, astasia and abnormal shape of the shoulders. Pathological examination of affected animals reveals hypoplasia of forelimb-girdle muscles with reduced diameter of muscle fibres. To identify the gene responsible for this disorder, we performed linkage mapping of the disorder locus using an inbred pedigree including a great-grand sire, a grand sire, a sire and 26 affected calves obtained from a herd of Japanese black cattle. Two hundred and fifty-eight microsatellite markers distributed across the genome were genotyped across the pedigree. Four markers on the middle region of bovine chromosome 26 showed significant linkage with the disorder locus. Haplotype analysis using additional markers in this region refined the critical region of the disorder locus to a 3.5-Mb interval on BTA26 between BM4505 and MOK2602. Comparative mapping data revealed several potential candidate genes for the disorder, including NRAP, PDZD8 and HSPA12A, which are associated with muscular function.

    DOI: 10.1111/j.1365-2052.2007.01679.x

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  • Suppressed recombination on mouse chromosome 15 defined regions of chromosomal inversions associated with koala (Koa) and hairy ears (Eh) mutations

    Kentaro Katayama, Aki Furuno, Sayaka Miyamoto, Miyuki Nakamura, Izurni Ojika, Yusuke Shinkai, Kouyou Akiyama, Takehito Tsuji, Tetsuo Kunieda

    EXPERIMENTAL ANIMALS   57 ( 1 )   73 - 77   2008.1

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    Koala (Koa) and hairy ears (Eh) mutations of mice are associated with chromosomal inversions in the distal half of chromosome 15. Since these two mutant mice show some common phenotypic features including extra hair on pinna and craniofacial dysmorphogenesis and have similar inverted regions, we determined the inverted regions of these two chromosomal inversions to examine whether a common gene is responsible for the phenotypes of these two mutants. The inverted regions were identified as the recombination-suppressed regions by linkage analysis. The length of the recombination-suppressed regions of Koa and Eh were approximately 52 and 47 Mb, respectively, and these inverted regions were not the same. These results indicate that the phenotypes of Koa and Eh mutant mice are likely to be caused by different genes.

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  • Short-limbed dwarfism: slw is a new allele of Npr2 causing chondrodysplasia

    Chizuru Sogawa, Takehito Tsuji, Yusuke Shinkai, Kentaro Katayama, Tetsuo Kunieda

    JOURNAL OF HEREDITY   98 ( 6 )   575 - 580   2007.9

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    Short-limbed dwarfism (SLW) is a new mutant mouse characterized by a dwarf phenotype with markedly short body, limbs, and tail. In the present study, we investigated the skeletal phenotypes of the SLW mouse and determined the chromosomal localization to identify the gene responsible for the phenotypes (s/w). Skeletal preparations stained with alcian blue and alizarin red revealed that longitudinal growth of the extremities of the affected (s/w/s/w) mice was significantly reduced in comparison with that of normal mice, whereas the positions and numbers of skeletal elements were normal. Histological examination of tibial growth plates of the affected mice showed that the numbers of proliferating and hypertrophic chondrocytes were obviously diminished. These phenotypes resembled to those of human chondrodysplasias caused by defective chondrocyte proliferation and differentiation. We mapped the s/w locus on an 11.7-cM interval of the proximal region of mouse chromosome 4 by linkage analysis. Furthermore, allelism test using Npr2(cn) locus, a mutant allele of Npr2 gene encoding a natriuretic peptide receptor B, revealed that s/w locus is an allele of the Npr2 gene. These results suggest that the dwarf phenotype of the SLW mouse is caused by the disturbed endochondral ossification, and a mutation in the Npr2 gene is expected to be responsible for the phenotypes of the SLW mouse.

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  • Limbinノックアウトマウスは軟骨内骨化の異常による骨成長遅延を呈する

    稲本政隆, 辻岳人, 神谷宣広, 三品裕司, 国枝哲夫

    日本骨代謝学会学術集会プログラム抄録集   25th   245 - 245   2007.6

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  • Characterization of chromosomal inversion of the mouse hairy ears (Eh) mutation associated with cleft palate

    Kentaro Katayama, Aki Furuno, Kouyou Akiyama, Takehito Tsuji, Tetsuo Kunieda

    MAMMALIAN GENOME   18 ( 4 )   246 - 254   2007.4

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    The hairy ears (Eh) mutation in the mouse originated from neutron irradiation experiments and is associated with chromosomal inversion on chromosome 15. Eh/+ mice have small pinna and extra hairs on the pinna but the phenotypic features of Eh/Eh mice are unclear. In this study we found that Eh/Eh mice died shortly after birth and had a cleft palate caused by impaired growth of palate shelves. Because genes located on the breakpoints of inversion are likely to be responsible for the defects associated with chromosomal inversions, we determined the breakpoints of the Eh inversion. We used a new genetic method that uses recombinant chromosomes resulting from crossing over between two overlapping inversions to determine the breakpoints. Koa is a mouse mutation associated with inversion of chromosome 15, which partially overlaps with the Eh inversion. We made Eh +/+ Koa double heterozygotes and obtained the recombinant chromosomes possessing deletion and duplication of the regions flanked by the breakpoints of both inversions, which were generated by crossing over within the overlapped region of these inversions. By defining the deleted regions we identified the breakpoints of the Eh inversion. We then examined the expression of genes in the vicinities of the breakpoints and found ectopic expression of the Hoxc5 gene and a transcript with unknown function in the developing palate of Eh/Eh mice, which is likely to be responsible for the cleft palate.

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  • Limbinのノックアウトマウスは軟骨低形成,短肢症を呈する~Ellis‐van Creveld syndromeの疾患モデルマウスの作成~

    神谷宣広, 竹田晴子, 辻岳人, 国枝哲夫, 三品裕司

    日本軟骨代謝学会プログラム・抄録集   20th   80   2007

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  • A mutation causing abnormal splicing of Tmem48/NdC1 gene is responsible for impaired gametogenesis in SKS mutant mouse.

    Kouyou Akiyama, Junko Noguchi, Mai Kanaeda, Takehito Tsuji, Tetsuo Kunieda

    BIOLOGY OF REPRODUCTION   90 - 90   2007

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  • CNP/NPRB plays an important role in follicular, development and oocyte maturation.

    Chiyo Iyosu, Takehito Tsuji, Tetsuo Kunieda

    BIOLOGY OF REPRODUCTION   115 - 116   2007

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  • A deletion in the endothelin-B receptor gene is responsible for the Waardenburg syndrome-like phenotypes of WS4 mice

    Shin Ohtani, Yusuke Shinkai, Akio Horibe, Kentaro Katayama, Takehito Tsuji, Yoshibumi Matsushima, Masayoshi Tachibana, Tetsuo Kunieda

    EXPERIMENTAL ANIMALS   55 ( 5 )   491 - 495   2006.10

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    The WS4 mouse is an animal model for human Waardenburg syndrome type 4 (WS4), showing pigmentation anomalies, deafness and megacolon, which are caused by defects of neural crest-derived cells. We have previously reported that the gene responsible for the WS4 mouse is an allele of the piebald mutations of the endothelin B receptor gene (Ednrb). In this study, we examined the genomi. c sequence of the Ednrb gene in WS4 mice and found a 598-bp deletion in the gene. The deleted region contains the entire region of exon 2 and the 5' part of exon 3 and is flanked by inverted repeat sequences which are suggested to trigger the deletion. We concluded that the deletion in the Ednrb gene is the causative mutation for the phenotype of WS4 mice.

    DOI: 10.1538/expanim.55.491

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  • Reduced expression of the endothelin receptor type B gene in piebald mice caused by insertion of a retroposon-like element in intron 1

    T Yamada, S Ohtani, T Sakurai, T Tsuji, T Kunieda, M Yanagisawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   281 ( 16 )   10799 - 10807   2006.4

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    Mice carrying the piebald mutation exhibit white coat spotting due to the regional absence of neural crest-derived melanocytes. We reported previously that the piebald locus encodes the Ednrb gene and that piebald mice express low levels of structurally intact Ednrb mRNA and EDNRB protein (Hosoda, K., Hammer, R. E., Richardson, J. A., Baynash, A. G., Cheung, J. C., Giaid, A., and Yanagisawa, M. (1994) Cell 79, 1267-1276). Here, we report that both the life span of the Ednrb mRNA and the promoter activity of the Ednrb gene are indistinguishable between wild-type and piebald mice. Introns 2-6 of the Ednrb gene in piebald mice were correctly excised with an efficiency indistinguishable from those in wild-type mice in exon trapping experiments. We found that the piebald allele of the Ednrb gene has a 5.5-kb retroposon-like element in intron 1 possessing canonical sequences of a polyadenylation signal and a splice acceptor site. Abnormal hybrid transcripts carrying exon 1 of the Ednrb gene and a portion of the 5.5-kb element are expressed in piebald mice. The insertion of the 5.5-kb element into a heterologous intron in a mammalian expression vector markedly reduced the expression of the reporter gene. Premature termination and aberrant splicing of the Ednrb transcript caused by the retroposon-like element in intron 1 lead to a reduced level of the normal Ednrb transcript, which is responsible for the partial loss-of-function phenotype of piebald mice.

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  • A PCR-RFLP method for identifying carriers of Hemophilia A in Japanese brown cattle

    Maryam Khalaj, Abdol Rahim Abbasi, Takehito Tsuji, Yasuo Moritomo, Kenichi Shimojo, Tetsuo Kunieda

    Anim. Sci. J.   2006

  • Linkage mapping of the locus responsible for congenital multiple ocular defects in cattle on bovine Chromosome 18

    AR Abbasi, N Ihara, T Watanabe, M Khalaj, T Tsuji, Y Sugimoto, T Kunieda

    MAMMALIAN GENOME   16 ( 9 )   731 - 737   2005.9

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    Congenital multiple ocular defects (MOD) in Japanese black cattle is a hereditary ocular disorder with an autosomal recessive manner of inheritance, showing developmental defects of the lens, retina, and iris, persistent embryonic eye vascularization, and microphthalmia. In the present study, we mapped the locus responsible for the disorder by linkage analysis using 240 microsatellite markers covering the entire bovine genome and an inbred pedigree obtained from commercial herds. The linkage analysis demonstrated a significant linkage between the disorder locus and markers on the proximal region of bovine Chromosome (BTA) 18 with the maximum LOD score of 5.1. Homozygosity mapping using the haplotype of the linked markers further refined the critical region. The results revealed the localization of the locus responsible for MOD in an approximately 6.6-cM region of BTA18. Comparison of published linkage and radiation hybrid (RH) maps of BTA18 with its evolutionary ortholog, human Chromosome (HSA) 16, revealed several potential candidate genes for the disorder including the MAF and FOXC2 genes.

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  • An insertion mutation of the bovine F11 gene is responsible for factor XI deficiency in Japanese black cattle

    M Kunieda, T Tsuji, AR Abbasi, M Khalaj, M Ikeda, K Miyadera, H Ogawa, T Kunieda

    MAMMALIAN GENOME   16 ( 5 )   383 - 389   2005.5

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    Factor XI deficiency in Japanese black cattle is an hereditary mild bleeding disorder with an autosomal recessive mode of inheritance. To characterize the molecular lesion causing factor XI deficiency in cattle, we isolated an entire coding region of the bovine F11 gene, which comprises 15 exons and 14 introns, and determined its nucleotide sequences. Comparison of the nucleotide sequences of the F11 gene between affected and unaffected animals revealed an insertion of 15 nucleotides in exon 9 of the affected animals. The insertion results in a substitution of one amino acid with six amino acids in a highly conserved amino acid sequence in the fourth apple domain of factor XI protein. Genotyping of the F11 gene in 109 Japanese black cattle revealed that the insertion clearly corresponded to the factor XI activities of the animals. We therefore concluded that the insertion of 15 nucleotides in the F11 gene is the causative mutation for factor XI deficiency in Japanese black cattle. Genotyping of the F11gene by detecting the insertion will be an effective DNA-based diagnostic system to prevent incidence of the disease.

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  • A loss-of-function mutation in natriuretic peptide receptor 2 (Npr2) gene is responsible for disproportionate dwarfism in cn/cn mouse

    T Tsuji, T Kunieda

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 14 )   14288 - 14292   2005.4

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    The achondroplastic mouse is a spontaneous mutant characterized by disproportionate dwarfism with short limbs and tail due to disturbed chondrogenesis during endochondral ossification. These abnormal phenotypes are controlled by an autosomal recessive gene (cn). In this study, linkage analysis using 115 affected mice of F-2 progeny mapped the cn locus on an similar to 0.8-cM region of chromosome 4, and natriuretic peptide receptor 2 (Npr2) gene was identified as the most potent candidate for the cn mutant in this region. This gene encodes a receptor for C-type natriuretic peptide (CNP) that positively regulates longitudinal bone growth by producing cGMP in response to CNP binding to the extracellular domain. Sequence analyses of the Npr2 gene in cn/cn mice revealed a T to G transversion leading to the amino acid substitution of highly conserved Leu with Arg in the guanylyl cyclase domain. In cultured chondrocytes of cn/cn mice, stimulus with CNP did not significantly increase intracellular cGMP concentration, whereas it increased in +/+ mice. Transfection of the mutant Npr2 gene into COS-7 cells also showed similar results, indicating that the missense mutation of the Npr2 gene in cn/cn mice resulted in disruption of the guanylyl cyclase activity of the receptor. We therefore concluded that the dwarf phenotype of cn/cn mouse is caused by a loss-of-function mutation of the Npr2 gene, and cn/cn mouse will be a useful model to further study the molecular mechanism regulating endochondral ossification by CNP/natriuretic peptide receptor B signal.

    DOI: 10.1074/jbc.C500024200

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  • Search for the genes regulating the longitudinal bone growth

    TSUJI Takehito, KIYOSU Chiyo, SOGAWA Chizuru, KUNIEDA Tetsuo

    The journal of animal genetics   32(2) 133-140 ( 2 )   133 - 140   2005

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    DOI: 10.5924/abgri2000.32.2_133

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  • 軟骨形成不全症モデル動物を用いた長管骨の成長を制御する遺伝子の解析

    辻 岳人

    岡山実験動物研究会報   2005

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  • Evidence for estrogen receptor expression in the bursal epithelial cells of chicks

    Young-Ha Shin, Fumiko Takagi, Sachi Sugita, Song Han, Takehito Tsuji, Asaki Abe, Yasuhiro Kondo

    Animal Science Journal   76 ( 3 )   255 - 259   2005

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    The aim of the present study was to demonstrate estrogen receptor (ER) α (ER-α) and ER-β expression in the bursa of Fabricius and cultured bursal epithelial cells (CBEC) by reverse transcription (RT)-polymerase chain reaction (PCR) using a primer set design based on the sequences of chicken ER-α complementary DNA (cDNA) and chicken ER-β-cDNA. In the case of ER-α, RT-PCR products of the expected size (698 base pairs (bp)) were amplified from cDNA derived from the bursa and CBEC, and from the oviduct, which was used as a positive control. All of the products were cleaved into two fragments of 476 bp and 222 bp by treating the products with restriction nuclease Hind III, indicating that these RT-PCR products from the bursa, CBEC and genital organs were the same. In contrast, in the case of ER-β, PCR products of the expected size (303 bp) were not detected in the bursa of Fabricius or CBEC, or in the oviduct and ovary. These results indicate that ER-α is expressed in the bursa of Fabricius and in CBEC, but ER-β is not expressed in the bursa or CBEC, or in the female genital organs of chickens.

    DOI: 10.1111/j.1740-0929.2005.00264.x

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  • A mutation in the serum and glucocorticoid-inducible kinase-like kinase (Sgkl) gene is associated with defective hair growth in mice

    K Masujin, T Okada, T Tsuji, Y Ishii, K Takano, J Matsuda, A Ogura, T Kunieda

    DNA RESEARCH   11 ( 6 )   371 - 379   2004.12

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    YPC is a mutant mouse strain with defective hair growth characterized by thin, short hairs and poorly developed hair bulbs and dermal papillae. To identify the gene associated with the phenotype, we performed genome-wide linkage analysis using 1010 backcross progeny and 123 microsatellite markers covering all chromosomes. The mutant locus (ypc) was mapped to a 0.2-cM region in the proximal part of mouse chromosome 1. This 0.2-cM region corresponds to a 450-kb region of genome sequence that contains two genes with known functions and five ESTs or predicted genes with unknown functions. Sequence analysis revealed a single C-to-A nucleotide substitution at nucleotide 1382 in the Sgkl gene, causing a nonsense mutation at codon 461. Sgkl encodes serum and glucocorticoid-inducible kinase-like kinase (SGKL), which belongs to a subfamily of serine/threonine protein kinases and has been suggested to have a role downstream of lipid signals produced by activation of phosphoinositide 3-kinase (PI3K). In the mutant SGKL, a serine residue in the C-terminal end of the protein (Ser486), which is indispensable for activation of SGKL upon phosphorylation, is abolished by premature termination. Specific expression of the Sgkl gene in the inner root sheath of growing hair follicles was also identified by in situ hybridization. Therefore, we concluded that the nucleotide substitution in the Sgkl gene is the causative mutation for defective hair growth in the ypc mutant mouse and that the signaling pathway involving SGKL plays an essential role in mammalian hair development.

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  • Expression of the Ellis-van Creveld (Evc) gene in the rat tibial growth plate

    T Tsuji, H Nakamura, A Hirata, T Yamamoto

    ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY   279A ( 2 )   729 - 735   2004.8

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    Ellis-van Creveld (EvC) syndrome is an autosomal recessive chondrodysplasia characterized by short limbs, postaxial polydactyly, natal teeth, and dysplastic nails. The Ellis-van Creveld (EVC) gene, which is mutated in patients with EvC syndrome, has been identified by positional cloning. However, the physiological roles of the EVC gene have not been elucidated. Histopathological analyses of EvC syndrome have shown disturbed chondrocytic phenotypes during cartilage development. We therefore postulated that the EVC gene is a critical factor for chondrocytes during endochondral ossification. The present study focuses on the relationship between the Evc gene and chondrocytes, and examines Evc gene expression in the rat tibial growth plate at the mRNA and protein levels. Evc mRNA in tibial epiphyseal cartilage was expressed at postnatal day (P) 1, P28, and P56 by RT-PCR. Immunohistochemical analyses localized the Evc protein mainly in prehypertrophic and hypertrophic chondrocytes of the epiphyseal growth plate in the tibia during the embryonic and postnatal periods. Evc mRNA was also detected in prehypertrophic and hypertrophic chondrocytes by in situ hybridization. These results indicate that the Evc gene functions mainly in the prehypertrophic and hypertrophic chondrocytes of the epiphyseal growth plate. The data presented here are important for future studies of the underlying mechanism of chondrodysplasia in EvC syndrome. (C) 2004 Wiley-Liss, Inc.

    DOI: 10.1002/ar.a.20059

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  • New mutant mouse with skeletal deformities caused by mutation in delta like 3 (DII3) gene

    Y Shinkai, T Tsuji, Y Kawamoto, T Kunieda

    EXPERIMENTAL ANIMALS   53 ( 2 )   129 - 136   2004.4

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    We have established a new mouse strain with vertebral deformities caused by an autosomal single recessive mutation (oma). The mutant mice showed short trunk and short and kinky tail. The skeletal preparations of newborn and prenatal mice showed disorganized vertebrae and numerous vertebral and rib fusions which are thought to be caused by patterning defects at the stage of somitegenesis. Linkage analysis localized the oma locus on the proximal region of mouse chromosome 7 close to DII3 gene. DII3 is the gene involved in the Notch signaling pathway and null-mutation of the gene has been reported to cause vertebral deformities. The phenotypic similarity between oma and DII3 null-mutant mice suggests that the causative gene for the oma mutant is the DII3 gene. We, therefore, investigated the nucleotide sequence of the DII3 gene of the oma mouse and found a single nucleotide substitution of G to T which causes missense mutation of glycine to cysteine at codon 409. Since the amino acid substitution is a nonconservative amino acid substitution at the conserved portion of the DII3 protein, and the substitution is specific to the mutant mice, we concluded that the nucleotide substitution of the DII3 gene is responsible for the skeletal deformities of the oma mouse.

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  • Ellis-van creveld症候群の原因遺伝子であるEvcとLbnの脛骨における発現について

    辻 岳人

    岡山大学農学部学術報告   2004

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  • 環境汚染物質の複合曝露が生体に及ぼす影響 -金属結合蛋白質metallothionein誘導を中心として-.

    十川紀夫, 十川千春, 辻 岳人, 山本敏男, 北山滋雄, 小野寺憲治

    応用薬理   2004

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  • Role of osteoclast extracellular signal-regulated kinase (ERK) in cell survival and maintenance of cell polarity

    H Nakamura, A Hirata, T Tsuji, T Yamamoto

    JOURNAL OF BONE AND MINERAL RESEARCH   18 ( 7 )   1198 - 1205   2003.7

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    Morphological changes of osteoclasts by a MEK1 inhibitor, PD98059,were investigated to clarify a role of ERK. PD98059 promoted apoptosis of osteoclasts and the loss of ruffled borders. This study supports the importance of ERK in survival and polarity of osteoclasts.
    Introduction: Extracellular signal-regulated kinase (ERK) is a mitogen activated protein kinase (MAPK) that has been reported to play a role in the survival and apoptosis of osteoclasts. However, the precise signal transduction mechanism is not fully understood. The aim of this study was to clarify the role of ERK in osteoclasts by histological analysis.
    Materials and Methods: Using a rat calvarial organ culture system, the inhibition of ERK phosphorylation by PD98059, a MAPK/ERK kinase 1 (MEK1) inhibitor, was assayed by immunoblotting. Morphological changes in osteoclasts induced by PD98059 were elucidated by light and electron microscopy. The cellular localization of ERK was also determined by immunoelectron microscopy.
    Results: PD98059 inhibited phosphorylated ERK after a 1-h incubation. Ultrastructural study demonstrated that PD98059 induced the accumulation of vesicles and vacuoles in osteoclasts and the loss of ruffled border at 1 h. At 3 h, some osteoclasts showed apoptosis with nuclear condensation, and at 6 h after PD98059 treatment, many osteoclasts were detached from the bone surface and had lost their cell polarity. Electron microscopic immunohistochemistry revealed that ERK was mainly localized in the cytoplasm of clear zones in control osteoclasts, but apoptotic osteoclasts also showed immunoreactivity in clear zone-like structures in contact with osteoblast-lineage cells.
    Conclusion: These findings indicate that ERK in osteoclasts is involved in their survival and may be involved in the formation of a ruffled border and the maintenance of cell polarity.

    DOI: 10.1359/jbmr.2003.18.7.1198

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  • Positional cloning of the gene LIMBIN responsible for bovine chondrodysplastic dwarfism

    H Takeda, M Takami, T Oguni, T Tsuji, K Yoneda, H Sato, N Ihara, T Itoh, Kata, SR, Y Mishina, JE Womack, Y Moritomo, Y Sugimoto, T Kunieda

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   99 ( 16 )   10549 - 10554   2002.8

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    Chondrodysplastic dwarfism in Japanese brown cattle is an autosomal recessive disorder characterized by short limbs. Previously, we mapped the locus responsible for the disease on the distal end of bovine chromosome 6. Here, we narrowed the critical region to approximate to2 cM by using linkage analysis, constructed a BAC and YAC contig covering this region, and identified a gene, LIMBIN (LBN), that possessed disease-specific mutations in the affected calves. One mutation was a single nucleotide substitution leading to an activation of a cryptic splicing donor site and the other was a one-base deletion resulting in a frameshift mutation. Strong expression of the Lbn gene was observed in limb buds of developing mouse embryos and in proliferating chondrocytes and bone-forming osteoblasts in long bones. These findings indicate that LBN is responsible for bovine chondrodysplastic dwarfism and has a critical role in a skeletal development.

    DOI: 10.1073/pnas.152337899

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  • Localization of osteoprotegerin (OPG) on bone surfaces and cement lines in rat tibia

    H Nakamura, T Tsuji, A Hirata, T Yamamoto

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   50 ( 7 )   945 - 953   2002.7

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    Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor (TNF) receptor family, is an osteoclastogenesis inhibitory factor. We investigated the localization of OPG in rat tibia using a specific peptide antibody to clarify the role of OPG in bone remodeling. OPG reactivity was mainly seen on bone surfaces. In bone matrices, OPG was also localized on cartilage/bone interfaces and cement lines. However, labeling was scarcely detected in the region of contact between osteoclasts and stromal cells. Some osteoblasts and osteocytes showed weak labeling. Immunoreactivity was not seen in chondrocytes or osteoclasts. Immunoelectron microscopic observation revealed that OPG is localized on the bone surfaces under osteoclasts. These findings suggest that OPG derived from osteoblast lineage cells and/or serum may be concentrated on resorbed bone surfaces and subsequently on cement lines. OPG may play an important role in the prevention of excess bone resorption by inhibiting differentiation and activity of osteoclasts in bone remodeling.

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  • Ultracytochemical study of medullary bone calcification in estrogen injected male Japanese quail

    T Yamamoto, H Nakamura, T Tsuji, A Hirata

    ANATOMICAL RECORD   264 ( 1 )   25 - 31   2001.9

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    Fine structural and cytochemical studies were performed to clarify the pattern of medullary bone calcification, specifically in relation to sulfated glycosaminoglycans, by using estrogen-induced medullary bone of male Japanese quails. Tibiae were collected at 4 and 7 days after estrogen treatment. Medullary bone had developed inward toward the marrow cavity, and calcification had begun near the cortical bone and deeper parts of the trabeculae, accompanied by wide osteoid at extending tips and surface areas of the trabeculae. Sulfated glycosaminoglycans, detected by high iron diamine (HID), were distributed in the matrix in a pattern similar to that of calcified matrix of the trabeculae. Cortical bone was negatively stained by HID. In undecalcified specimens, calcified nodules were seen in areas undergoing calcification. Globular structures composed of fine filamentous materials, a marginal dense layer, and central core, were also observed in the matrix of decalcified specimens. Both the calcified nodules and globular structures showed the same distribution pattern, i.e., they were dispersed at surface areas and coalesced in the deeper areas of the matrix. The globular structures were exclusively positive for HID-thiocarbohydrazide-silver protein (HID-TCH-SP) stain, indicating the localization of sulfated glycosaminoglycans. These results strongly suggest that medullary bone calcification progresses by the coalescence of calcified nodules and that sulfated glycosaminoglycans play an important role for the regulation of globular calcification. Anat Rec 264:25-31, 2001. (C) 2001 Wiley-Liss, Inc.

    DOI: 10.1002/ar.1101

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  • The insulin receptor-related receptor (Insrr) gene maps to mouse chromosome 3

    T Tsuji, H Katoh, T Kunieda

    EXPERIMENTAL ANIMALS   50 ( 4 )   359 - 360   2001.7

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    DOI: 10.1538/expanim.50.359

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  • Immunolocalization of keratan sulfate proteoglycan in rat calvaria

    H Nakamura, A Hirata, T Tsuji, T Yamamoto

    ARCHIVES OF HISTOLOGY AND CYTOLOGY   64 ( 1 )   109 - 118   2001.2

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    We investigate, by the immunogold method, the localization of keratan sulfate (KS) proteoglycan in rat calvaria in order to clarify the detailed process of intramembranous ossification. KS was localized in bone nodules corresponding to calcified nodules, close to the saggital suture of calvaria, The immunoreactivity decreased in fully calcified regions distant from the suture. Electron microscopic observation revealed that KS was distributed in and around matrix vesicles, among collagen fibrils at the initial crystal deposition stage, and then concentrated in bone nodules. According to the progress of mineralization, KS tended to be localized in the peripheral region of the nodules. In addition, these nodules came in contact with collagen fibrils which also showed KS-positive reactivity. In cell organelles of osteoblasts, KS was detected in the Golgi apparatus. These findings suggest that osteoblasts in intramembranous ossification sites actively synthesize KS. IIS in the calcified nodules, as well as other glycosaminoglycans in osteoid, may play an important role in additional and/or collagenous calcification by trapping calcium ions through its negative charge.

    DOI: 10.1679/aohc.64.109

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  • Cloning of the Promoter Region and Expression Analysis of Mouse Insulin Receptor-related Receptor (Irr) Gene

    TSUJI Takehito, SATO Katsunori, KUNIEDA Tetsuo

    Nihon Chikusan Gakkaiho   72 ( 2 )   169 - 171   2001

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    In the present study, we isolated promoter region of mouse insulin receptor-related receptor (Irr) gene and analyzed its expression in various mouse tissues and embryos in different stages. The nucleotide sequence of the promoter region of the Irr gene showed the presence of putative promoter elements and binding sites for trans-acting factors. The expression analysis revealed the strong expression in kidney, stomach, and embryo at the stage of 14.5 days. These findings were basically consistent with the previously reported findings of rat and human, but we found several differences in the sequence and expression pattern of the gene between mouse and rat or human.

    DOI: 10.2508/chikusan.72.169

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  • The down-regulated in adenoma (Dra) gene encoding intestine-specific anion transporter maps to mouse chromosome 12

    T Kunieda, K Takahashi, Y Shinkai, T Tsuji, CW Schweinfest, H Katoh

    EXPERIMENTAL ANIMALS   49 ( 1 )   67 - 68   2000.1

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    DOI: 10.1538/expanim.49.67

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  • Cloning and Mapping of the Mouse Gpx2 gene Encoding Gastrointestinal Glutathione Peroxidase

    Takehito Tsuji, Yuka Watanabe, Hideki Katoh, Katsunori Sato, Tetsuo Kunieda

    Journal of Veterinary Medical Science   60 ( 5 )   651 - 654   1998

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    Language:English   Publisher:Maruzen Co. Ltd.  

    Gastrointestinal glutathione peroxidase (GSHPx-GI) is an enzyme expressed in intestinal epithelial cells and may reduce hydroperoxides generated from the ingested diet. We isolated a genomic clone containing the mouse Gpx2 gene encoding 190 amino acids of GSHPx-GI. This gene is composed of two exons and an intron. The nucleotide sequence of the coding region was 89.9% identical with that of the human GPX2 gene. A TGA opal codon predicted to encode a selenocysteine was identified at codon 40. A genomic clone containing a pseudogene for the Gpx2 gene was also isolated. The nucleotide sequence of the pseudogene was 98.3% identical with that of the mouse Gpx2 gene and showed characteristics of a processed pseudogene. Linkage analysis using backcross mouse progeny indicated the mouse Gpx2 gene and its pseudogene to be located on mouse chromosomes 12 and 7, respectively.

    DOI: 10.1292/jvms.60.651

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  • Cloning and Mapping of the Mouse Gpx2 gene Encoding Gastrointestinal Glutathione Peroxidase

    Takehito Tsuji, Yuka Watanabe, Hideki Katoh, Katsunori Sato, Tetsuo Kunieda

    Journal of Veterinary Medical Science   60 ( 5 )   651 - 654   1998

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    Language:English   Publisher:Maruzen Co. Ltd.  

    Gastrointestinal glutathione peroxidase (GSHPx-GI) is an enzyme expressed in intestinal epithelial cells and may reduce hydroperoxides generated from the ingested diet. We isolated a genomic clone containing the mouse Gpx2 gene encoding 190 amino acids of GSHPx-GI. This gene is composed of two exons and an intron. The nucleotide sequence of the coding region was 89.9% identical with that of the human GPX2 gene. A TGA opal codon predicted to encode a selenocysteine was identified at codon 40. A genomic clone containing a pseudogene for the Gpx2 gene was also isolated. The nucleotide sequence of the pseudogene was 98.3% identical with that of the mouse Gpx2 gene and showed characteristics of a processed pseudogene. Linkage analysis using backcross mouse progeny indicated the mouse Gpx2 gene and its pseudogene to be located on mouse chromosomes 12 and 7, respectively.

    DOI: 10.1292/jvms.60.651

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  • A Mutation in Endothelin-B Receptor Gene Causes Myenteric Aganglionosis and Coat Color Spotting in Rats

    Tetsuo Kunieda, Taeko Kumagai, Takehito Tsuji, Tsuyoshi Ozaki, Hideaki Karaki, Hiroshi Ikadai

    DNA Research   3 ( 2 )   101 - 105   1996

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    Language:English   Publisher:Universal Academy Press Inc.  

    Congenital aganglionosis rat (AR) is a mutant with an autosomal recessive gene (sl), which shows megacolon caused by the absence of myenteric ganglion cells and white coat-color with a small pigmented spot on the head. Recently, targeted disruption of the endothelin-B (ETB) receptor gene (EDNRB) in the mouse has been reported to cause aganglionic megacolon and coat color spotting resembling the phenotypes of the sl/sl rats. To identify the mutation responsible for the phenotypes of the sl/sl rats, we determined the nucleotide sequences of the EDNRB genes of the sl/sl rats and found that a 301-bp region intervening between direct repeat sequences was deleted in the EDNRB gene, and the deletion produces various transcripts due to aberrant splicing.

    DOI: 10.1093/dnares/3.2.101

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  • A Mutation in Endothelin-B Receptor Gene Causes Myenteric Aganglionosis and Coat Color Spotting in Rats

    Tetsuo Kunieda, Taeko Kumagai, Takehito Tsuji, Tsuyoshi Ozaki, Hideaki Karaki, Hiroshi Ikadai

    DNA Research   3 ( 2 )   101 - 105   1996

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    Language:English   Publisher:Universal Academy Press Inc.  

    Congenital aganglionosis rat (AR) is a mutant with an autosomal recessive gene (sl), which shows megacolon caused by the absence of myenteric ganglion cells and white coat-color with a small pigmented spot on the head. Recently, targeted disruption of the endothelin-B (ETB) receptor gene (EDNRB) in the mouse has been reported to cause aganglionic megacolon and coat color spotting resembling the phenotypes of the sl/sl rats. To identify the mutation responsible for the phenotypes of the sl/sl rats, we determined the nucleotide sequences of the EDNRB genes of the sl/sl rats and found that a 301-bp region intervening between direct repeat sequences was deleted in the EDNRB gene, and the deletion produces various transcripts due to aberrant splicing.

    DOI: 10.1093/dnares/3.2.101

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Presentations

  • 骨成長をもたらす突然変異(dwg)の原因遺伝子の同定

    第30回日本骨代謝学会  2012 

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  • Mad2l2遺伝突然変異がおよぼすDNA損傷修復機構への影響

    第35回日本分子生物学会  2012 

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  • 矮小を呈するstbマウスの組織学的解析および原因遺伝子のマッピング

    第30回日本骨代謝学会  2012 

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  • sks突然変異マウスのパキテン期精母細胞における核の形態異常

    日本実験動物学会総会  2011 

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  • Roles of Syntaxin2/Epimorphin (Stx2/Epim) in progression of meiosis during mouse spermatogenesis

    2nd World Congress on Reproductive Biology  2011 

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  • Cloning of candidate genes for TMEM48 binding proteins, which could be involved in gametogenesis.

    Society for the study of reproduction 43rd annual meeting  2010 

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  • repro34突然変異マウスを用いたStx2/Epim遺伝子の精子形成における機能の解析

    第57回日本実験動物学会  2010 

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  • マウス精巣においてTMEM48/NDC1と相互作用するタンパク質の探索

    第57回日本実験動物学会  2010 

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  • The role of Stntaxin2/Epimorphin (Stx2/Epinm) in progression of meisis during dpermatogenesis.

    Society for the study of reproduction 43rd annual meeting  2010 

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  • DWARFISM AND CATARACTS IN MICE WITH dwg LOCUS ARE CAUSED BY THE MUTATUION IN Ggt1 GENE

    Mouse Genetics & Genomics:Development & Disease.  2009 

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  • 骨成長不全および白内障をもたらす突然変異(dwg)の原因遺伝子の同定

    第56回日本実験動物学会総会  2009 

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  • 見島牛における和牛の諸形質に関与する遺伝子変異の解析

    本動物遺伝育種学会第10回記念大会  2009 

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  • Identification of a mutation in the gamma-glutamyl transferase 1 (Ggt1) gene causing dwarfism and cataracts in dwg/dwg mice

    23nd International Mammalian Genome Conference  2009 

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  • Stx2/Epim遺伝子の突然変異により精子形成に異常を呈するrepro34マウスの解析

    第102回日本繁殖生物学会  2009 

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  • 排卵過程におけるエンドセリンファミリーの役割について

    第9回日本動物遺伝育種学会  2008 

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  • 精子形成が減数分裂第一分裂前期で停止するENU誘発突然変異repro23マウスの解析

    第9回日本動物遺伝育種学会  2008 

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  • 精子形成に特異的なSpata4遺伝子の機能の解析

    第9回日本動物遺伝育種学会  2008 

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  • Hypomorphic mutation in mouse Nppc gene causes retarded bone growth due to impaired endochondral ossification

    22nd International Mammalian Genome Conference  2008 

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  • Npr2変異マウスにおける脂肪重量減少についての解析

    第55回日本実験動物学会総会  2008 

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  • 減数分裂第一分裂前期で精子形成が停止するENU 誘発突然変異(repro23 )マウスの解析

    第55回日本実験動物学会総会  2008 

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  • FKBP6欠損ラット(TTラット)の精母細胞に出現するリボソーム集塊の原因解析

    第100回日本繁殖生物学会大会  2007 

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  • 生殖生命科学研究のためのモデル動物の確立

    第24回日本疾患モデル学会総会  2007 

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  • Limbinノックアウトマウスは軟骨内骨化の異常による骨成長遅延を呈する

    第25回日本骨代謝学会  2007 

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  • Thtマウスにおける初期胚の発生停止と染色体逆位

    第54回日本実験動物学会  2007 

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  • FKBP6欠損ラット(TTラット)の精母細胞に出現するリボゾーム集塊の原因解析

    第54回日本実験動物学会  2007 

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  • Linkage mapping of locus responsible for Forelimb-girdle Muscular Anomaly of japanse black cattle on BTA26

    第107回日本畜産学会  2007 

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  • ミュータントマウスを用いた卵胞形成におけるCNP/NPRB の機能の解析

    第24回日本疾患モデル学会総会  2007 

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  • CNP/NPRB plays an important roles in follicular development and oocyte maturation.

    Society for the study of reproduction 40Th annual meeting  2007 

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  • A mutation causing abnormal splicing of Tmem48/NdC1 gene is responsible for impaired gametogenesis in SKS mutant mouse.

    Society for the study of reproduction 40Th annual meeting  2007 

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  • Limbinのノックアウトマウスは軟骨低形成、短肢症を呈する〜Ellis-van Creveld syndromeの疾患モデルマウスの作製〜

    第20回日本軟骨代謝学会  2007 

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  • 骨格異常を呈するThtマウスの連鎖解析および表現型の解析

    第53回日本実験動物学会  2006 

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  • 骨格および配偶子形成に異常を呈するミュータントマウスにおける新規膜貫通タンパク質遺伝子の突然変異

    第53回日本実験動物学会  2006 

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  • Edmrb遺伝子の挿入レトロトランスポゾンの欠失により生じたpiebald復帰突然変異体

    第53回日本実験動物学会  2006 

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  • マウスjaggedtail(jg)突然変異の染色体マッピングおよび形態学的解析

    第23回日本疾患モデル動物学会  2006 

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  • Ehマウスが呈する口蓋裂の発生機構および原因遺伝子の解析

    第23回日本疾患モデル動物学会  2006 

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  • piebald 復帰突然変異体におけるエンドセリンBレセプター遺伝子の解析

    第22回日本疾患モデル学会  2005 

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  • アロキサン誘発糖尿病感受性とIdd10遺伝子座との関連について

    第22回日本疾患モデル学会  2005 

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  • SLWマウスにおけるCNPレセプター(NPRB)欠損が消化管に与える影響

    第22回日本疾患モデル学会  2005 

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  • NPRB変異マウス(cn/cn)の雌における生殖機能の解析

    第22回日本疾患モデル学会  2005 

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  • 軟骨形成不全症を呈する突然変異(cn/cn)マウスの原因遺伝子の同定

    第28回日本分子生物学会  2005 

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  • Natriuretic peptide receptor 2 遺伝子におけるミスセンス変異は長管骨の成長障害をもたらす

    第23回日本骨代謝学会  2005 

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  • 矮小を呈するSLWマウスにおける原因遺伝子の同定

    第52回日本実験動物学会  2005 

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  • Cloning of bovine F8 gene and a mutation associated with factor VIII deficiency of Japanese brown cattle

    第104回日本畜産学会  2005 

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  • Comparative mapping of bovine chromosome 18 revealed candidate genes for bovine multiple ocular defects

    第104回日本畜産学会  2005 

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  • A loss-of-function mutation in natriuretic peptide receptor 2 (Npr2) gene is responsible for mouse achondroplasia.

    第18回マウスゲノム会議  2004 

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  • Linkage mapping of the locus responsible for bovine congenital eye anomaly on the bovine choromosome 18.

    第29回 国際動物遺伝学会議  2004 

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  • Cloning of bovine F11 gene and identification of a mutation responsible for factor XI deficiency of Japanese black cattle

    第29回 国際動物遺伝学会議  2004 

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  • 新規矮小マウス(SLW)における形態学的解析と原因遺伝子のマッピング

    第51回日本実験動物学会総会  2004 

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  • 被毛異常ミュータントマウスの原因となるSgkl遺伝子における突然変異

    第21回日本疾患モデル動物学会  2004 

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  • A mutation in the serum and glucocorticoid-inducible kinase-like kinase (Sgkl) gene is responsible for defective hair growth in mice.

    第18回マウスゲノム会議  2004 

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  • An insertion of a retrotransposon in the Ednrb gene cause piebald coat color of the s/s mouse.

    第18回マウスゲノム会議  2004 

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  • 毛色異常突然変異piebald(s)におけるEdnrb遺伝子へのレトロトランスポゾンの挿入

    第51回日本実験動物学会総会  2004 

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  • 黒毛和種における血液凝固第XI因子欠乏症の遺伝子診断法の確立

    第103回日本畜産学会  2004 

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  • 雄性仮性半陰陽ラット(mp/mp)における原因遺伝子の同定

    第20回日本疾患モデル学会  2003 

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  • 環境汚染物質の複合曝露が生体に及ぼす影響 -金属結合蛋白質metallothionein 誘導を中心として-

    第5回応用薬理シンポジウム  2003 

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  • Eh(Hairy ear)マウスにおける染色体逆位の切断点の決定

    第50回日本実験動物学会  2003 

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  • Identification of the breakpoints of choromosomal inversions in Hairy Ear (EH) and Koala (KOA) mutant mice.

    国際マウスゲノム会議  2003 

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  • 四肢短縮小人症Ellis-van Creveled症候群の原因遺伝子EVCとIHHの成長板軟骨におけ る発現

    第25回日本分子生物学会  2002 

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  • エナメル芽細胞におけるExtracellular signal-regulated kinase (ERK) に関する形 態学的研究

    第44回歯科基礎医学会学術大会  2002 

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  • Positional cloning of a novel gene, LIMBIN, responsible for a bovine chondrodysplastic dwarfism.

    第28回 国際動物遺伝学会議  2002 

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  • 破骨細胞のExtracellular Signal Regulated kinase (ERK)に関する形態学的解析

    第20回骨代謝学会  2002 

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  • Positional cloning of a novel gene, LIMBIN, responsible for a bovine chondrodysplastic dwarfism.

    第25回分子生物学会  2002 

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  • 四肢短縮小人症Ellis-van Cleveled症候群の遺伝子であるEVC遺伝子の軟骨細胞にお ける発現

    第20回骨代謝学会  2002 

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  • 破骨細胞におけるMAPkinase系ERKに関する形態学的解析

    第107回日本解剖学会  2002 

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  • 吸収骨表面、セメントラインにおけるオステオプロテジェリン局在

    第43回歯科基礎医学会  2001 

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  • MAP kinase系ERKは破骨細胞の波状縁形成を制御する

    第19回日本骨代謝学会  2001 

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  • 鳥類の骨髄骨におけるオステオポンチンの免疫組織化学的研究

    第106回日本解剖学会  2001 

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  • 骨組織におけるオステオプロテジェリン局在

    第106回日本解剖学会総会  2001 

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  • ウズラ骨髄骨基質のケラタン硫酸と石灰化

    第105回日本解剖学会  2000 

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  • 骨髄骨石灰化におけるケラタン硫酸とsulferの分布について

    第42回歯科基礎医学会  2000 

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  • Animal Science Laboratory Practicum 2-2 (2020academic year) Second semester  - 木5,木6,木7,木8

  • Molecular Genetics of Mammals (2020academic year) Late  - その他

  • Specific Research of Science for Bio-Production (2020academic year) Year-round  - その他

  • Seminars in Special Field of Study 1 (2020academic year) 1st and 2nd semester  - その他

  • Seminars in Special Field of Study 2 (2020academic year) 3rd and 4th semester  - その他

  • New development of gene engineering (2020academic year) Third semester  - 木3,木4

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