Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans.
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.
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.
Takatoshi
T
Hikida
Hanna
H
Jaaro-Peled
Saurav
S
Seshadri
Kenichi
K
Oishi
Caroline
C
Hookway
Stephanie
S
Kong
Di
D
Wu
Rong
R
Xue
Manuella
M
Andradé
Stephanie
S
Tankou
Susumu
S
Mori
Michela
M
Gallagher
Koko
K
Ishizuka
Mikhail
M
Pletnikov
Satoshi
S
Kida
Akira
A
Sawa
D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers; D004195:Disease Models, Animal; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*
D015415:Biomarkers; C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins