2016 Fiscal Year Final Research Report
Association analysis of the molecular basis of brain development and mouse behavior using CAMDI knockout mice
| Project/Area Number |
26460495
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | CAMDI / HDAC6 / 自閉症 / 中心体 / 治療 / 細胞移動 |
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| Outline of Final Research Achievements |
CAMDI has been suggested to promote radial migration through centrosome regulation. However, its physiological relevance is unclear. We report the generation and characterization of CAMDI-deficient mice. CAMDI-deficient mice exhibit delayed radial migration with aberrant neural circuit formation and psychiatric behaviors including hyperactivity, repetitive behavior, and social abnormality typically observed in autism spectrum disorder patients. Analyses of direct targets of CAMDI identify HDAC6 whose a-tubulin deacetylase activity is inhibited by CAMDI at the centrosome. CAMDI deficiency increases HDAC6 activity, leading to unstable centrosomes with reduced c-tubulin and acetylated α-tubulin levels. Most importantly, psychiatric behaviors as well as delayed migration are significantly rescued by treatment with Tubastatin A, a specific inhibitor of HDAC6.
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| Free Research Field |
脳・神経科学
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