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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.

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


Authors

J. Dachtler

J.L. Ivorra

T.E. Rowland

R.J. Rodgers

S.J. Clapcote



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

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Publisher Licence URL
http://creativecommons.org/licenses/by/3.0/

Copyright Statement
© 2015 The Author(s) This article has been published under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s). Author(s) grant(s) the American Psychological Association the exclusive right to publish the article and identify itself as the original publisher.






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