The role of a candidate gene in the etiology of autism spectrum disorder

2015 Fiscal Year Final Research Report

• Project/Area Number: 24500452
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• 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)
• Co-Investigator(Kenkyū-buntansha): TOCHIGI Mamoru 帝京大学, 医学部, 准教授 (40456116)
• Project Period (FY): 2012-04-01 – 2016-03-31
• 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

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.

Free Research Field

神経化学　精神医学