| Project/Area Number |
14370332
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Okazaki National Research Institutes |
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Principal Investigator |
MOROHASHI Ken-ichirou Okazaki National Research Institute, National Institute for Basic Biology, Division Of Cell Differentiation, Professor, 基礎生物学研究所, 教授 (30183114)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUI Yuuko Okazaki National Research Institute, National Institute for Basic Biology, Division of Cell Differentiation, Research Associate, 基礎生物学研究所, 助手 (50342639)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2002: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | Ad4BP / SF-1 / Nuclear Receptor / ARX / Gonad / Gene Disrupted Mouse / SUMO / Sex / 転写因子 / 細胞極性 / 性分化 |
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| Research Abstract |
Gonad is the tissue showing the most prominent sexual difference. Moreover, the gonad induces sex differentiation of other tissues through production of sex steroid hormones. The following studies were performed to elucidate the molecular mechanisms underlying gonad sex differentiation.
(1)Vinexine was isolated as a protein interacting with Ad4BP/SF-1. Since the expression was detected in the developing fetal gonads, the gene KO mouse was generated and the phenotype was examined. Interestingly, the KO mouse showed XY sex reversal and phosphorylation of ERK was reduced significantly in the male fetal gonad.
(2)Functions of a homeo box protein, Arx, were examined with the gene KO mouse, and found that Arx is involved in Leydig cell differentiation. Moreover, the gene mutation was found to cause a human disease, X-linked lissencephaly with abnormal genitalia.
(3)With respect to posttranslational modification of Ad4BP/SF-1, we revealed that Ad4BP/SF-1 is SUMOylated and phosphorylated. SUMOylation suppressed transcriptional activity. Interestingly, Sox9 was also SUMOylated and the SUMOylation of these two transcription factors suppressed their synergistic transcription of the MIS gene. The effects of phosphorylation is still under investigation.
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