Heterozygous deletion of ?-neurexin I or ?-neurexin II results in behaviors relevant to autism and schizophrenia.

ABSTRACT: The neurexins are a family of presynaptic cell adhesion molecules. Human genetic studies have found heterozygous deletions affecting NRXN1 and NRXN2, encoding ?-neurexin I (Nrxn1?) and ?-neurexin II (Nrxn2?), in individuals with autism spectrum disorders and schizophrenia. However, the link between ?-neurexin deficiency and the manifestation of psychiatric disorders remain unclear. To assess whether the heterozygous loss of neurexins results in behaviors relevant to autism or schizophrenia, we used mice with heterozygous (HET) deletion of Nrxn1? or Nrxn2?. We found that in a test of social approach, Nrxn1? HET mice show no social memory for familiar versus novel conspecifics. In a passive avoidance test, female Nrxn1? HET mice cross to the conditioned chamber sooner than female wild-type and Nrxn2? HET mice. Nrxn2? HET mice also express a lack of long-term object discrimination, indicating a deficit in cognition. The observed Nrxn1? and Nrxn2? genotypic effects were specific, as neither HET deletion had effects on a wide range of other behavioral measures, including several measures of anxiety. Our findings demonstrate that the heterozygous loss of ?-neurexin I and ?-neurexin II in mice leads to phenotypes relevant to autism and schizophrenia.

SUBMITTER: Dachtler J 

PROVIDER: S-EPMC4655861 | biostudies-other | 2015 Dec

REPOSITORIES: biostudies-other