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2003 Fiscal Year Final Research Report Summary

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
Keywordssex-determination / SRY / SOX / claudin11 / testis / HSFY / azoospermic
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

  • Research Products

    (19 results)

All Other

All Publications (19 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2005-04-19  

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