抄録
Offer Organization: Japan Society for the Promotion of Science, System Name: Grants-in-Aid for Scientific Research, Category: Grant-in-Aid for Scientific Research (C), Fund Type: -, Overall Grant Amount: - (direct: 4100000, indirect: 1230000)
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.