3D reconstruction of the outer surface of the brains of wild type (+/+) and Zic2 knockdown (kd/+) mice with lateral ventricle (green). Dorsal (left) and anterior-lateral (right) views are indicated. Note the enlarged lateral ventricles and the narrowed interspace between the left and right lateral ventricles containing septum (asterisk). ZIC2 has been known as a causal gene for holoprosencephaly and encodes a zinc-finger-type transcriptional regulator. We characterized Zic2 knockdown mice with a moderate (40%) reduction in Zic2 expression. Zic2 knockdown mice also showed increased locomotor activity in novel environments, cognitive and sensorimotor gating dysfunctions, and social behavioral abnormalities. Because these features are reminiscent of schizophrenia, we examined ZIC2 variant in schizophrenia patients. A novel missense mutation in ZIC2 (R409P) in schizophrenia patients was found to lower transcription-activating capacity, and to impair target DNA-binding and co-factor-binding capacities. These results warrant further study of ZIC2 in the pathogenesis of schizophrenia. Original Article Japanese Introduction