2002 Fiscal Year Final Research Report Summary
Analysis of molecules involved in mouse primordial germ cell development
| Project/Area Number |
13670216
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Osaka University |
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Principal Investigator |
KIMURA Tohru Research Institute for Microbial Diseases, Osaka University, Associate Professor, 微生物病研究所, 助教授 (50280962)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Toru Research Institute for Micobial Diseases, Osaka University, Professor, 微生物病研究所, 教授 (00172370)
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| Project Period (FY) |
2001 – 2002
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| Keywords | primordial germ cells / EG cells / PTEN / pluripotency / stem cells / tumor suppressor |
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| Research Abstract |
In order to gain insights into the germ cell development in mammals, we have generated and analyzed (1) mouse germ cell-less homologue (mgcl-1) deficient mice and (2) mice lacking PTEN tumor suppressor in primordial germ cells
(1) Spermatogenesis is a process of drastic structural and functional reorganization of nucleus. mgcl-1 encodes a nuclear lamine-associated protein highly expressed during the process. We demonstrate that severe morphological abnormalities of sperm and consequent impaired fertility occur in mgcl-1 null male mice. Defective nuclear envelope integrity precedes deregulated chromatin remodeling and deformed nuclear morphogenesis in the mutant mice, showing that mgcl-1 is an essential component for nuclear-lamina organization in sperm nuclear remodeling. Thus, mgcl-1 null mice provide a unique model of "laminopathy" such as Emery-Dreifuss muscular dystrophy, which is caused by the mutation of nuclear envelope components.
(2) Primordial germ cells (PGCs) are committed to the germ lineage but maintain the potential to de-differentiate into pluripotent embryonic germ (EG) cells. Using PGC-specific Pten-null mice, we demonstrated that the PTEN tumor suppressor plays an important role in regulating PGC differentiation in vivo and in vitro. Male mice lacking PTEN exhibited bilateral testicular teratoma resulting from impaired mitotic arrest, loss of germ cell differentiation properties, and regain of immature cell characteristics. Experiments in culture revealed a greater proliferative capacity and higher EG cell colony-forming ability in Pten-null PGCs. This was attributable, at least in part, to de-differentiation from germ-line-committed cells into pluripotent cells. Our results suggest that PTEN is a critical regulator of germ cell differentialion.
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Research Products
(12 results)
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[Publications] Tanaka R, Yoshida A, Murakami T, Baba E, Lichtenfeld J, Omori T, Kimura T, Tsurutani N, Fujii N, Wang Z-X, Pepier SC, Yamamoto N, and Tanaka Y.: "Unique monoclonal antibody recognizing the third extracellular loop of the human CXCR4 induces lymphocyte agglutination and enhances human immunodeficiency virus type-1-mediated syncytium formation and productive infection"J. Virol.. 75(23). 11534-11543 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sato M, Kimura T, Kurokawa K, Fujita Y, Abe K, Masuhara M, Yasunaga T, Ryo A, Yamamoto M, and Nakano T.: "Identification of PGC7, a new gene expressed specifically in preimplantation embryos and germ cells"Mech. Dev.. 113(1). 91-94 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Kimura T, Ito C, Watanabe S, Takahashi T, Ikawa M, Yomogida K, Fujita Y, Ikeuchi M, Asada N, Matsumiya K, Okuyama A, Okabe M, Toshimori K, and Nakano T.: "Mouse germ cell-less as en essential component for nuclear integrity"Mol. Cell. Biol.. 23 (4). 1304-1315 (2003)
Description
「研究成果報告書概要(欧文)」より
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