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MOLECURA and GENETIC ANALYSIS OF THE SEX-DETERMININC CASCADE RELATED WITH SRY

Research Project

Project/Area Number 13672377
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human genetics
Research InstitutionThe University OF Tokushima

Principal Investigator

SHINKA Toshikatsu  The UNIVERSITY TOKUSHIMA, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE OF PROFESSOR, 医学研究科, 助教授 (10311820)

Co-Investigator(Kenkyū-buntansha) NAKAHORI Yutaka  The UNIVERSITY TOKUSHIMA, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 医学研究科, 教授 (10172389)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Keywordssex-determination / SRY / SOX / claudin11 / testis / HSFY / azoospermic / SOX9 / セルトリー細胞 / NT2 / D1細胞 / Cos1細胞 / SOX9プロモーター / Claudin11プロモーター / 転写活性 / SRY過剰発現 / SR / HMG box / two hybrid system / ERα / ERβ / 相互作用 / 性分化 / ヒト
Research Abstract

The sex differentiation of the gonad is a cascade which requires many different gene expressions. In male, SRY triggers male-specific gonadal differentiation in the fetal stage. However, so far, genes which SRY/SOX directly regulate remain unclear. It has been reported that claudinll which belong to the claudin family, the important component of tight junction (TJ), is expressed in fetal Sertoli cells after Sry expression. To elucidate whether human claudin11 expression is affected with SRY/SOX, we cloned 1.1kb 5'flanking region of the human claudin11 gene and characterized it. Over-expression of SRY or SOX9 in the NT2/D1 cells activated the human claudin11 promoter up to 2.5 and 1.7 times, respectively, compared to the controls. Furthermore, we found that claudin11 gene expression was increased in the NT2/D l cells which stably over-expressed FLAG-tagged SRY Our findings demonstrate that SRY or SOX may affect the formation of TJs between Sertoli cells during testis development through the regulation of claudin11
During this project, we became to be interested in HSFY which is located on the Y chromosome and have a HSF-type DNA binding domain, since functions of HSFY was unclear. when we screened for deletions on the Yq of males suffering from infertility, we found that HSFY was involved in interstitial deletions on the Y chromosomes for two azoospermic males who had DBY, USP9Y and, DAZ but did not have RBMY located on the AZFb. Expression analysis of HSFY unveiled that they are expressed predominantly in testis. Furthermore, immunnohistochemistry of HSFY in testis showed that its expression is restricted to both Sertoli cells and spermatogenic cells, and that it exhibits a stage-dependent translocation from the cytoplasm to the nucleus in spermatogenetic cells during spermatogenesis. These results may suggest that deletion of HSFY is involved in azoospermia or oligospermia

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Shinka T et al.: "Molecular Characterization of Heat Shock-like Factor Encoded on the Human Y Chromosome, and Implications for Male Infertility"Biology of Reproduction. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chen G et al.: "Roles of estrogen receptor α (ERα) in the regulation of the human Mullerian inhibitory substance (MIS) promoter"Journal of Medical investigation. 50. 192-198 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jin H.J et al.: "Y-chromosomal DNA haplogroups and their implications for the dual origins of the Koreans"Human Genetics. 114. 27-35 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jabasini, M et al.: "Range of separation of potential tool for bioseparation, Microchip electrophoresis system, for DNA polymorphisms on the Y chromosome"Analytical Sciences. 19. 175-176 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lettice LA et al.: "Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly"Proc Natl Acad Sci U S A. 99. 7548-7553 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinka, T et al.: "A rapid and simple method for sex identification by heteroduplex analysis, using denaturing high- performance liquid chromatography (DHPLC)"Journal of Human Genetics. 46. 263-266 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 新家利一, 中堀 豊: "小児疾患のとらえかた(男も女も元は一緒)"浅井宏祐. 399 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee, J.W et al.: "Y-chromosome compound haplotypes with the microsatellite markers DXYS265, DXYS266, and DXYS241"J.Hum.Genet.. 46. 80-84 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinka, T et al.: "A rapid and simple method for sex identification by heteroduplex analysis, using denaturing high performance liquid chromatography (DHPLC)"J.Hum.Genet.. 46. 263-266 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ewis, A.A et al.: "Occupational cancer genetics : Infrequent ras oncogenes point mutations in lung cancer samples from chromate workers"Amer.J.Indust.Med.. 40. 92-97 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ewis, A.A et al.: "Two Y-chromosome specific polymorphisms 12f2 and DFFRY in the Japanese population and their relations to other Y-polymorphisms"J.Med.Invest.. 49. 44-50 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ewis, A.A et al.: "Linkage between prostate cancer incidence a polymorphism DYS19"J.Med.Invest.. 49. 56-60 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ewis, A.A et al.: "Microdeletions of a Y-specific marker, Yfm l, and implications for a role in spermatogenesis"J Hum Genet.. 47. 257-261 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lettice LA et al.: "Disruption of a long-range cis-acting regulator for Shh causes preaxialpolydactyly"Proc Natl Acad Sci U S A. 99. 7548-7553 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ewis A.A et al.: "Yfm1, a multi-copy marker, specific for the Y chromosome and beneficial for forensic, population genetic and spermatogenesis-related studies"J.Hum.Genet.. 47. 523-528 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jabasini, M et al.: "Range of separation of potential tool for bioseparation, Microchip electrophoresis system, for DNA polymorphisms on the Y chromosome"Analytical Sciences.. 19. 175-176 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jin HJ et al.: "Y chromosomal DNA haplogroups and their implications for the dual origins of the Koreans"Hum Genet.. 114. 27-35 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gang Chen et al.: "Roles of estrogen receptor α (ERα) in the regulation of the human Mullerian inhibitory substance (MIS) promoter"J.Med.Invest.. 50. 192-198 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinka T.: "Molecular Characterization of Heat Shock like Factor Encoded on the Human Y Chromosome, and Implications for Male Infertility"Biol Reprod. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinka T et al.: "Molecular Characterization of Heat Shock-like Factor Encoded on the Human Y Chromosome, and Implications for Male Infertility"Biology of Reproduction. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chen G et al.: "Roles of estrogen receptor α (ERα) in the regulation of the human Mullerian inhibitory substance (MIS) promoter"Journal of Medical investigation. 50. 192-198 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jin H.Jet al.: "Y-chromosomal DNA haplogroups and their implications for the dual origins of the Koreans"Human Genetics. 114. 27-35 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jabasini, M et al.: "Range of separation of potential of potential tool for bioseparation, Microchip electrophoresis system, for DNA polymorphisms on the Y chromosome"Analytical Sciences. 19. 175-176 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 新家利一, 中堀 豊: "小児疾患のとらえかた(男も女も元は一緒)"浅井宏祐. 399 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ewis, A.A.: "Two Y-chromosome-specific polymorphisms 12f2 and DFFRY in the Japanese population and heir relations to other Y-polymorphisms"J. Med. Invest. 49. 44-50 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ewis, A.A.: "Microdeletions of a Y-specific marker, Yfm1, and implications for a role in spermatogenesis"J Hum. Genet. 47. 523-528 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ewis A.A.: "Yfm1, a multi-copy marker, specific for the Y chromosome and beneficialforforensic population genetic and spermatogenesis-related studies"J Hum. Genet.. 47. 523-528 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Jabasini, M.: "Analysis of DNA polymorphisms on the human Y-chromosome by microchip electrophoresis"Electrophoresis. 23. 1537-1542 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Lettice LA: "Disruption of a long-range cis-acting regulator for Shh causes preaxialpolydactyly"Proc Natl Acad Sci USA. 99. 7548-7453 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Lee, J.W.: "Y-chromosome compound haplotypes with the microsatellite markers DXYS265, DXYS266 and DXYS241."J Hum Genet.. 46. 80-84 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinka, T.: "A rapid and simple method for sex identification by analysis of a heteroduplex using denaturing high performance liquid chromatography(DHPLC)."J Hum Genet.. 46. 263-266 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ewis, A.A.: "Occuptional cancer genetics : Infrequent ras oncogenes point mutations in lung cancer samples from chromate workers. Amer."J. Indust. Med.. 40. 92-97 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ewis, A.A.: "Two Y-chromosome-specific polymorphisms 12f2 and DFFRY in the Japanese population and their relations to other Y polymorphisms."J. Med. Invest.. 49(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ewis, A.A.: "Linkage between prostate cancer incidence and different alleles of the human Y-linked tetranucleotide polymorphism DYS19."J. Med. Invest.. 49(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Jabasini, M.: "Fast Analysis of DNA Polymorphims on the Human Y Chromosome by Using Microchip Electrophoresis."Electrophoresis. 23(in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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