| 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)
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| 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
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