Dominant-negative DISC1 transgenic mice displayed schizophrenia-associated phenotypes, including enlarged lateral ventricles, reduced parvalbumin immunoreactivity, and behavioral abnormalities.
Does transgenic expression of dominant-negative DISC1 in mice induce schizophrenia-associated phenotypes?
DN-DISC1 transgenic mice exhibit anatomical, histological, and behavioral phenotypes relevant to schizophrenia, providing a useful preclinical model for studying the disease.
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.
Hikida et al. (Sat,) conducted a other in Schizophrenia (animal model). Dominant-negative DISC1 (DN-DISC1) transgene vs. Wild-type (wt) littermates was evaluated on Anatomical and behavioral schizophrenia-associated phenotypes. Dominant-negative DISC1 transgenic mice displayed schizophrenia-associated phenotypes, including enlarged lateral ventricles, reduced parvalbumin immunoreactivity, and behavioral abnormalities.