| Project/Area Number |
14580738
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TEZUKA Tohru The University of Tokyo, The Institute of Medical Science, Div. Oncology, Research Associate, 医科学研究所, 助手 (50312319)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Src / tyrosine phosphorylation / NMDA receptor / Knock-in Mice / DNA Chip Analysis / チロシンキナーゼ / NR2A / NR2B / 記憶・学習 / リン酸化 / Fyn / ノックインマウス |
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| Research Abstract |
To elucidate the roles of NMDAR tyrosine phosphorylation by Src, we established NR2B Y1472F knock-in mice in which Tyr-1472, a major tyrosine phosphorylation site of NR2B, is mutated to Phenylalanine. Mutant mice were highly crossed with C57BL/6 for electrophysiological and be-havioral analyses. These mutant mice showed impairment in amygdaloid LTP and auditory fear conditioning. We also isolated ES cell clones aimed to the most prominent tyrosine phosphoryla-tion site on NR2A. Electrophysiological analyses using reconstituted NRlINR2A(Wild type and YF mutants) and recombinant Src are underway. Although we generated rabbit polyclonal anti-bodies that specifically recognize phosphorylated NR2A or NR2B, they are applicatable only for western blotting. We are trying to generate better antibodies. PSD-95, a scaffold protein for NMDAR, was also tyrosine-phosphorylated in the brain, and the level of its phosphorylation was reguced in Fyn KO mice. Fyn KO mice show several neural defects including NMDAR-depen-dent synaptic plasticity and myelination. To analyse these phenotypes from the view of gene expression, we compared the gene expression profile in the brain between WT and Fyn KO mice. In addition, we carded out characterization of a novel brain-enriched kinase BREK.
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