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-l (Nrg-l) as a candidate susceptibility gene for schizophrenia. We examined the behavior of mice heterozygous for a mutation in neuregulin-l's immunoglobulin (Ig)-like domain (lg-nrg-l (+/-) 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-l mutants, lg-nrg-l (+/-) mice did not exhibit significantly elevated locomotion relative to littermate controls. These results suggest that lg-Nrg-l's contribute to some - but not all - aspects of the schizophrenia-like phenotype of nrg-l mutants, and further support nrg-l as a candidate gene for schizophrenia. (c) 2005 Lippincott Williams & Wilkins.