Grid2 dependent regulation of BDNF

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670155
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: TAKEMORI Hiroshi 独立行政法人医薬基盤研究所, 創薬基盤研究部, プロジェクトリーダー (90273672)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: Grid2 / BDNF / 運動記憶 / 遺伝学 / マイクロサテライト解析

Outline of Final Research Achievements

We identified a mouse strain with a naturally occurring mutation and an ataxic phenotype that presents with severe leg cramps. To investigate the phenotypes of these mutant mice, we screened several phenotype-modulating drugs and found that memantine (10 mg/kg) disrupted the sense of balance in the mutants. Moreover, the mutant mice showed an attenuated optokinetic response (OKR) and impaired OKR learning, which was also observed in wild-type mice treated with memantine. Microsatellite analyses indicated that the Grid2 gene-deletion is responsible for these phenotypes. Patch-clamp analysis showed a relatively small change in NMDA-dependent current in cultured granule cells from Grid2 gene-deleted mice, suggesting that GRID2 is important for correct NMDA receptor function.In addition, Grid2 mutant mice expressed abnormal BDNF protein, suggesting tat Grid2 mutant mice is helpful to analyze NMDA-R related memory.

Free Research Field

遺伝学