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

Dachtler, J.; Ivorra, J.L.; Rowland, T.E.; Lever, C.; Rodgers, R.J.; Clapcote, S.J.

Abstract

The neurexins are a family of presynaptic cell adhesion molecules. Human genetic studies have found heterozygous deletions affecting NRXN1 and NRXN2, encoding α-neurexin I (Nrxn1α) and α-neurexin II (Nrxn2α), in individuals with autism spectrum disorders and schizophrenia. However, the link between α-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 Nrxn1α or Nrxn2α. We found that in a test of social approach, Nrxn1α HET mice show no social memory for familiar versus novel conspecifics. In a passive avoidance test, female Nrxn1α HET mice cross to the conditioned chamber sooner than female wild-type and Nrxn2α HET mice. Nrxn2α HET mice also express a lack of long-term object discrimination, indicating a deficit in cognition. The observed Nrxn1α and Nrxn2α 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 α-neurexin I and α-neurexin II in mice leads to phenotypes relevant to autism and schizophrenia.

Citation

Dachtler, J., Ivorra, J., Rowland, T., Lever, C., Rodgers, R., & Clapcote, S. (2015). Heterozygous deletion of α-neurexin I or α-neurexin II results in behaviors relevant to autism and schizophrenia. Behavioral Neuroscience, 129(6), 765-776. https://doi.org/10.1037/bne0000108

• Journal Article Type: Article
• Acceptance Date: Sep 22, 2015
• Online Publication Date: Dec 1, 2015
• Publication Date: Dec 1, 2015
• Deposit Date: Apr 15, 2016
• Publicly Available Date: May 3, 2016
• Journal: Behavioral Neuroscience
• Print ISSN: 0735-7044
• Electronic ISSN: 1939-0084
• Publisher: American Psychological Association
• Peer Reviewed: Peer Reviewed
• Volume: 129
• Issue: 6
• Pages: 765-776
• DOI: https://doi.org/10.1037/bne0000108
• Public URL: https://durham-repository.worktribe.com/output/1384232