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.