Neuregulin-1 immunoglobulin-like domain mutant mice: clozapine sensitivity and impaired latent inhibition.
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.
Rimer
Mendell
M
Section of Neurobiology, University of Texas at Austin, Austin, TX 78712-0248, USA. rimer@mail.utexas.edu
Barrett
Douglas W
DW
Maldonado
Monica A
MA
Vock
Vita M
VM
Gonzalez-Lima
F
F
D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000502:physiology; D003024:Clozapine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D007136:Immunoglobulins; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D020890:Neuregulin-1 / Q000737:chemistry* / Q000235:genetics*; D010641:Phenotype; D017434:Protein Structure, Tertiary / Q000502:physiology; D012420:Running; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D007136:Immunoglobulins; D020890:Neuregulin-1; D003024:Clozapine