Ca2+-dependent activator protein for secretion 2 and autistic-like phenotypes

Ca2+-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.