Mice carrying a schizophrenia-associated mutation of the Arhgap10 gene are vulnerable to the effects of methamphetamine treatment on cognitive function: association with morphological abnormalities in striatal neurons

Abstract We recently found a significant association between exonic copy-number variations in the Rho GTPase activating protein 10 ( Arhgap10 ) gene and schizophrenia Japanese patients. Special attention was paid to one patient carrying missense variant (p.S490P) exon 17, which overlapped with an deletion other allele. Accordingly, we generated mouse model S490P/NHEJ mice) coexisting frameshift mutation. examined spatiotemporal expression of mRNA brain highest levels cerebellum, striatum, nucleus accumbens (NAc), followed by frontal cortex adolescent mice. The phosphorylated myosin phosphatase-targeting subunit 1 p21-activated kinases striatum NAc were significantly increased mice compared wild-type littermates. exhibited increase neuronal complexity spine density NAc. There no difference touchscreen-based visual discrimination learning mice, but impairment evident not when they treated methamphetamine. number c-Fos-positive cells after methamphetamine treatment dorsomedial core Taken together, these results suggested that schizophrenia-associated mutations result morphological abnormality neurons NAc, may be associated vulnerability cognition treatment.