Previous studies show that mice with Ywhae deficiency show abnormalities in brain development including defects in neuronal migration of post-mitotic pyramidal neurons as well as neuronal differentiation and proliferation in neuronal progenitor cells. Also, our previous research indicated that the Ywhae knockout mice show moderate defects in working memory and anxiety-like behavior. This previous work was performed using heterozygous mutant mice. Here we performed behavioral analyses using homozygous Ywhae knockout mice and found that the homozygous Ywhae knockout mice have increased locomotor activity, decreased working memory, and increased sociability. Taken together with the results obtained from the previous pathophysiological analyses in the Ywhae knockout mice, the Ywhae knockout mouse is useful for pathophysiological analyses of neuropsychiatric disorders caused by defects during neurodevelopment.