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Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans.

Authors:
Hikida T, Jaaro-Peled H, Seshadri S, Oishi K, Hookway C, Kong S, Wu D, Xue R, Andradé M, Tankou S, Mori S, Gallagher M, Ishizuka K, Pletnikov M, Kida S, Sawa A
Affiliation:
Journal:
Proceedings of the National Academy of Sciences of the United States of America

Abstract

Here, we report generation and characterization of Disrupted-In-Schizophrenia-1 (DISC1) genetically engineered mice as a potential model for major mental illnesses, such as schizophrenia. DISC1 is a promising genetic risk factor for major mental illnesses. In this transgenic model, a dominant-negative form of DISC1 (DN-DISC1) is expressed under the alphaCaMKII promoter. In vivo MRI of the DN-DISC1 mice detected enlarged lateral ventricles particularly on the left side, suggesting a link to the asymmetrical change in anatomy found in brains of patients with schizophrenia. Furthermore, selective reduction in the immunoreactivity of parvalbumin in the cortex, a marker for an interneuron deficit that may underlie cortical asynchrony, is observed in the DN-DISC1 mice. These results suggest that these transgenic mice may be used as a model for schizophrenia. DN-DISC1 mice also display several behavioral abnormalities, including hyperactivity, disturbance in sensorimotor gating and olfactory-associated behavior, and an anhedonia/depression-like deficit.

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