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Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14501-6. Epub 2007 Aug 3.

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

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1
Department of Psychiatry and Behavioral Sciences, Graduate Program in Cellular and Molecular Medicine, and Division of Neurobiology, The Johns Hopkins University, Baltimore, MD 21287, USA.

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.

PMID:
17675407
PMCID:
PMC1964873
DOI:
10.1073/pnas.0704774104
[Indexed for MEDLINE]
Free PMC Article
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