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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.

Pubmed ID: 17675407

Authors

  • 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

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

September 4, 2007

Associated Grants

  • Agency: NIMH NIH HHS, Id: MH-069853
  • Agency: NIA NIH HHS, Id: P01-AG-017688

Mesh Terms

  • Animals
  • Behavior, Animal
  • Biological Markers
  • Disease Models, Animal
  • Genes, Dominant
  • Humans
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Phenotype
  • Schizophrenia