| Project/Area Number |
24500452
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
YASUDA Shin 公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, 研究員 (20392368)
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| Co-Investigator(Kenkyū-buntansha) |
TOCHIGI Mamoru 帝京大学, 医学部, 准教授 (40456116)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 自閉スペクトラム症 / 樹状突起スパイン / 16p11.2微細欠失 / TAO2キナーゼ / 16p11.2症候群 / 海馬 / 16p11.2 / 自閉症スペクトラム障害 / シナプス可塑性 / カドヘリン / 自閉症モデル / 神経可塑性 / 自閉症 / 遺伝子発現 |
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| Outline of Final Research Achievements |
Dendritic filopodia are most abundant during early phase of synaptogenesis, but the number of filopodia declines thereafter. When filopodia contact presynaptic sites and form synapses, filopodia convert into dendritic spines. Normal dendritic spinogenesis may be related to learning and memory function, and abnormal spine formation may cause the autistic spectrum disorder (ASD).TAO2b is a p38 MAP kinase kinase kinase, which binds to a protocadherin arcadlin at its cytoplasmic region. The gene encoding TAO2b is known to be located on chromosome 16p11.2, a region has been shown to carry substantial susceptibility to ASD. To address if TAO2b variants are associated with ASD, we sequenced TAO2b in patients and unaffected individuals. We identified two rare TAO2b variants in ASD individuals. Overexpression of each variant caused dendritic spine abnormality in cultured hippocampal neurons. We generated TAO2b knock mice. Tao2b knockout induced aberrant spine morphology and ASD-like behavior.
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