| Project/Area Number |
09308028
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Mie University |
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Principal Investigator |
SAKAKURA Teruyo Mie University, Faculty of Medicine, Professor, 名誉教授 (80073120)
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| Co-Investigator(Kenkyū-buntansha) |
NINOMIYA Yoshifumi Okayama University, Faculty of Medicine, Professor, 医学部, 教授 (70126241)
KUSAKABE Moriaki Tsukuba Life Science Center, Physical and Chemical Research, Chief investigator, 実験動物室, 室長 (60153277)
YOSHIDA Toshimichi Mie University, Faculty of Medicine, Professor, 医学部, 教授 (80166959)
NODA Masaharu Molecular Neurobiology, National Basic Biology, Professor, 基礎生物学研究所, 教授 (60172798)
KIMATA Kouji Aichi Medical University, Biomedical Research Center, Professor, 分子医科学研究所, 教授 (10022641)
岡山 実 京都産業大学, 工学部, 教授 (90158816)
大平 敦彦 愛知県心身障害コロニー, 発達障害研究所, 部長 (20101074)
北川 泰雄 名古屋大学, 生物分子応答研究センター, 教授 (50101168)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥30,500,000 (Direct Cost: ¥30,500,000)
Fiscal Year 1999: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1998: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1997: ¥13,100,000 (Direct Cost: ¥13,100,000)
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| Keywords | anti-adhesion / extracellular matrix / jean-targeted mice / Integrin / Syndecan / Annexin / cell growth / cell migration / ノックアウトマウス / ノックインマウス / 細胞接着 / 細胞抗接着 / 抗一接着 / 形態形成 / 細胞分化 / 神経発生 / 癌転移 |
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| Research Abstract |
The purpose of this research project is to elucidate the molecular and biological mechanisms of anti-adhesion ECMs particularly by use of transgenic animals and genetically altered cells. The results for three years are as follows.
1) Production of transgenic mice and their analysis
* Establishment of tenascin-C knockout (TNKO) inbred strains (Kusakabe, Sakakura). Demonstration of low mammary tumor incidence in TKNO-GR and -C3H mice (Yoshida, Sakurai), delayed wound healing and disturbed regeneration (Kusakabe), and abnormal behaviors and neurotransmitters (Kusakabe).
* Production of PTPz knockin mice and demonstration of its expression in neurons as well as glial cells (Noda).
* Production of Col4A6 knockout mice and demonstration of Alport syndrome like changes, but not leiomyomatosis (Ninomiya).
* Studies are undergoing on proteoglycans (Okayama, Kimata), neuroglycans (Oohira) and laminins (Kitagawa).
2) Determination of the anti-adhesive domains
* By use of libraries of monoclonal antibodies against tenascin-C, the growth stimulation was identified at EGF-like domain (Kusakabe) and at alternative spliced domain (Yoshida). Anti-adhesion site is not determined yet.
* Annexin VI (Kimata) and syndecan 2 (Okayama) are the cell surface receptors, and laminin a4 chain (Kitagawa) is the ligand of anti-adhesive proteoglycans.
* PTPz (Noda) and neuroglycan (Oohira) are migration stimulating for neuronal cells in culture.
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