Neuregulin-1 immunoglobulin-like domain mutant mice: clozapine sensitivity and impaired latent inhibition

Neuroreport. 2005 Feb 28;16(3):271-5. doi: 10.1097/00001756-200502280-00014.

Abstract

Genetic and behavioral studies in humans and mouse mutants have implicated the gene encoding neuregulin-1 (Nrg-1) as a candidate susceptibility gene for schizophrenia. We examined the behavior of mice heterozygous for a mutation in neuregulin-1's immunoglobulin (Ig)-like domain (Ig-nrg-1 mice). We found that these animals displayed behaviors related to a schizophrenia-like phenotype, such as clozapine suppression of open-field and running wheel activity and impaired latent inhibition. Contrary to findings with other nrg-1 mutants, Ig-nrg-1 mice did not exhibit significantly elevated locomotion relative to littermate controls. These results suggest that Ig-Nrg-1's contribute to some - but not all - aspects of the schizophrenia-like phenotype of nrg-1 mutants, and further support nrg-1 as a candidate gene for schizophrenia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antipsychotic Agents / therapeutic use*
  • Behavior, Animal / physiology
  • Clozapine / therapeutic use*
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Immunoglobulins
  • Mice
  • Mice, Mutant Strains
  • Motor Activity / drug effects
  • Neural Inhibition / drug effects*
  • Neuregulin-1 / chemistry*
  • Neuregulin-1 / genetics*
  • Phenotype
  • Protein Structure, Tertiary / physiology
  • Running
  • Schizophrenia / drug therapy*

Substances

  • Antipsychotic Agents
  • Immunoglobulins
  • Neuregulin-1
  • Clozapine