| Project/Area Number |
12470026
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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 |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
NAKANO Toru Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, 微生物病研究所, 教授 (00172370)
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| Co-Investigator(Kenkyū-buntansha) |
木村 透 大阪大学, 微生物病研究所, 助手 (50280962)
鈴木 聡 大阪大学, 微生物病研究所, 講師 (10311565)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥16,400,000 (Direct Cost: ¥16,400,000)
Fiscal Year 2001: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2000: ¥10,800,000 (Direct Cost: ¥10,800,000)
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| Keywords | Primordial germ cell / Spermatogenesis / Teratoma / Embryonic germ cell / PTEN / Germ cell-less / Oogenesis / 遺伝子破壊 / 細胞分化 / PTEN |
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| Research Abstract |
To reveal the molecular basis of stem cells, we analyzed the function of three genes and found that all of them are essential for germ line stem cell systems.
1) We analyzed the function of a tumor suppressor gene PTEN (phosphatase and tensin homologue from chromosome 10). PTEN is a negative regulator of P13kinase by its phosphatase activity catalyzing from PIP3 to PIP2. We produced primordial germ cell (PGC) specific PTEN targeting mouse. The PGC specific PTEN null mice showed teratoma formation in all new born male mice. And the in vitro proliferative activity and embryonic germ cell forming activity was strikingly increased in the null mice.
2) We cloned a mouse homologue of Drosophila germ cell less gene which is essential for PGC formation in the fly. To analyze the function of the gene (mouse germ cell less-1, mgcl-1), gene targeting mice were produced. The mice did not show any abnormality in PGC formation. However, the fertility of the targeting mice was significantly reduced. During the study, it was reported that mgcl-1 protein binds to a component of nuclear envelope, LAP2β, which prompted us to examine the nuclear morphology in spermatogenesis. Nuclear morphology of the null spermatocyte was abnormal and subsequent chromatin remodeling was impaired.
3) Piwi is a gene essential for germ cell self renewing activity in Drosophila. We cloned one mouse homologue, mili, and analyzed its function by gene targeting. The mili null mice could not produce sperm due to apoptotic cell death at pachytene phase of primary spermatocytes.
All of the results facilitates the understanding of molecular mechanisms of stem cells in germ system.
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