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

Takatoshi Hikida, Hanna Jaaro-Peled, Saurav Seshadri, Kenichi Oishi, Caroline Hookway, Stephanie Kong, Di Wu, Rong Xue, Manuella Andradé, Stephanie Tankou, Susumu Mori, Michela Gallagher, Koko Ishizuka, Mikhail Pletnikov, Satoshi Kida, Akira Sawa

Research output: Contribution to journalArticlepeer-review

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 αCaMKII 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.

Original languageEnglish (US)
Pages (from-to)14501-14506
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number36
DOIs
StatePublished - Sep 4 2007

Keywords

  • Depression
  • MRI
  • Model
  • Parvalbumin
  • Translational

ASJC Scopus subject areas

  • General

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