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J Clin Invest. 2007 Apr;117(4):931-43. Epub 2007 Mar 22.

Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients.

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Laboratory for Molecular Neurogenesis and Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.


Autism, characterized by profound impairment in social interactions and communicative skills, is the most common neurodevelopmental disorder, and its underlying molecular mechanisms remain unknown. Ca(2+)-dependent activator protein for secretion 2 (CADPS2; also known as CAPS2) mediates the exocytosis of dense-core vesicles, and the human CADPS2 is located within the autism susceptibility locus 1 on chromosome 7q. Here we show that Cadps2-knockout mice not only have impaired brain-derived neurotrophic factor release but also show autistic-like cellular and behavioral phenotypes. Moreover, we found an aberrant alternatively spliced CADPS2 mRNA that lacks exon 3 in some autistic patients. Exon 3 was shown to encode the dynactin 1-binding domain and affect axonal CADPS2 protein distribution. Our results suggest that a disturbance in CADPS2-mediated neurotrophin release contributes to autism susceptibility.

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