Autistic-like behavioral phenotypes in a mouse model with copy number variation of the CAPS2/CADPS2 gene

Ca2+-dependent activator protein for secretion 2 (CAPS2 or CADPS2) facilitates secretion and trafficking of dense-core vesicles. Recent genome-wide association studies of autism have identified several microdeletions due to copy number variation (CNV) in one of the chromosome 7q31.32 alleles on which the locus for CAPS2 is located in autistic patients. To evaluate the biological significance of reducing CAPS2 copy number, we analyzed CAPS2 heterozygous mice. Our present findings suggest that adequate levels of CAPS2 protein are critical for normal brain development and behavior, and that allelic changes due to CNV may contribute to autistic symptoms in combination with deficits in other autism-associated genes.

► CAPS2 protein levels in heterozygous mice were reduced to half of that in wild-type. ► Heterozygous mice exhibited decreased locomotion following exposure to a novel object. ► Ultrasonic calls emitted by heterozygous pups were fewer than those of wild-type. ► Heterozygous mice exhibited deficits in intrinsic sleep–wake regulation.