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

Mark McIntosh,'s picture
PubMed URL: 
http://www.ncbi.nlm.nih.gov/pubmed/17675407
Author: 
Sawa A
Author List: 
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
Journal: 
Proc Natl Acad Sci U S A
PubMed ID: 
17675407
Pagination: 
14501-6
Volume: 
104
Issue: 
36
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.
Published Date: 
September, 2007

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