Ca(2+)-dependent activator protein for secretion 2 (CAPS2 or CADPS2) regulates dense-core vesicle (DCV) exocytosis. We found that CAPS2 is involved in the secretion of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and that CAPS2 KO mice not only have deficits in neuronal development and survival but also exhibit abnormal behaviors, including impaired social interaction, hyperactivity, an abnormal sleep-wake rhythm and increased anxiety in unfamiliar environments. Moreover, we identified increased expression of a rare CAPS2 splice variant in autism patients that specifically lacks exon 3 and that is not transported to axons when exogenously expressed in mouse cortical neurons. Moreover, non-synonymous SNPs have been identified in some autistic patients. These results implicate CAPS2 in autism susceptibility. Therefore, CAPS2 KO mice will be a useful animal model to study the aspects of the neuropathology and behavior characteristics of neurodevelopmental disorders.
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