Research on human genetics of schizophrenia enables to discover effective targets for its diagnosis and medication because of its high heritability. Rare or de novo copy-number variations (CNVs) are likely the most significant contributors to the pathogenesis of schizophrenia. We recently found novel schizophrenia-associated CNVs including ARHGAP10. ARHGAP10 is a member of the Rho GTPase-activating protein (RhoGAP) family that contributes to organizing the actin skeleton, as well as neuronal polarization. We developed a mouse model of schizophrenia patient with both a deletion-type CNV and a single-nucleotide variation (SNV) in the RhoGAP domain of ARHGAP10 gene (ARHGAP10 mutant mice). The mutant mice showed emotional abnormality and potentiation of psychostimulant-induced hyperlocomotion. Furthermore, psychostimulant-treated ARHGAP10 mutant mice showed a marked reduction of percentage of accuracy compared with psychostimulant-treated wild-type mice as well as saline-treated ARHGAP10 mutant mice in a translatable visual discrimination task that reflects cognitive function. These findings suggest that mutations in ARHGAP10 increase the risk of schizophrenia, and Rho signaling pathway may be a potential therapeutic target to develop novel antipsychotics.