Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.

<h4>Background</h4>Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy number of multiple genes, but deletions at 2p16.3, which have been associated with autism, schizophrenia and mental retardation, a...

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Autores principales:	Hannah Mary Grayton, Markus Missler, David Andrew Collier, Cathy Fernandes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/572a5183b1af4c6f8167db5aec08bb69
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spelling	oai:doaj.org-article:572a5183b1af4c6f8167db5aec08bb692021-11-18T07:39:32ZAltered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.1932-620310.1371/journal.pone.0067114https://doaj.org/article/572a5183b1af4c6f8167db5aec08bb692013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23840597/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy number of multiple genes, but deletions at 2p16.3, which have been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, usually the alpha isoform. Previous analyses of neurexin 1α (Nrxn1α) knockout (KO) mouse as a model of these disorders have revealed impairments in synaptic transmission but failed to reveal defects in social behaviour, one of the core symptoms of autism.<h4>Methods</h4>We performed a detailed investigation of the behavioural effects of Nrxn1α deletion in mice bred onto a pure genetic background (C57BL/6J) to gain a better understanding of its role in neurodevelopmental disorders. Wildtype, heterozygote and homozygote Nrxn1α KO male and female mice were tested in a battery of behavioural tests (n = 9-16 per genotype, per sex).<h4>Results</h4>In homozygous Nrxn1α KO mice, we observed altered social approach, reduced social investigation, and reduced locomotor activity in novel environments. In addition, male Nrxn1α KO mice demonstrated an increase in aggressive behaviours.<h4>Conclusions</h4>These are the first experimental data that associate a deletion of Nrxn1α with alterations of social behaviour in mice. Since this represents one of the core symptom domains affected in autism spectrum disorders and schizophrenia in humans, our findings suggest that deletions within NRXN1 found in patients may be responsible for the impairments seen in social behaviours, and that the Nrxn1α KO mice are a useful model of human neurodevelopmental disorder.Hannah Mary GraytonMarkus MisslerDavid Andrew CollierCathy FernandesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e67114 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hannah Mary Grayton Markus Missler David Andrew Collier Cathy Fernandes Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
description	<h4>Background</h4>Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy number of multiple genes, but deletions at 2p16.3, which have been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, usually the alpha isoform. Previous analyses of neurexin 1α (Nrxn1α) knockout (KO) mouse as a model of these disorders have revealed impairments in synaptic transmission but failed to reveal defects in social behaviour, one of the core symptoms of autism.<h4>Methods</h4>We performed a detailed investigation of the behavioural effects of Nrxn1α deletion in mice bred onto a pure genetic background (C57BL/6J) to gain a better understanding of its role in neurodevelopmental disorders. Wildtype, heterozygote and homozygote Nrxn1α KO male and female mice were tested in a battery of behavioural tests (n = 9-16 per genotype, per sex).<h4>Results</h4>In homozygous Nrxn1α KO mice, we observed altered social approach, reduced social investigation, and reduced locomotor activity in novel environments. In addition, male Nrxn1α KO mice demonstrated an increase in aggressive behaviours.<h4>Conclusions</h4>These are the first experimental data that associate a deletion of Nrxn1α with alterations of social behaviour in mice. Since this represents one of the core symptom domains affected in autism spectrum disorders and schizophrenia in humans, our findings suggest that deletions within NRXN1 found in patients may be responsible for the impairments seen in social behaviours, and that the Nrxn1α KO mice are a useful model of human neurodevelopmental disorder.
format	article
author	Hannah Mary Grayton Markus Missler David Andrew Collier Cathy Fernandes
author_facet	Hannah Mary Grayton Markus Missler David Andrew Collier Cathy Fernandes
author_sort	Hannah Mary Grayton
title	Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
title_short	Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
title_full	Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
title_fullStr	Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
title_full_unstemmed	Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
title_sort	altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/572a5183b1af4c6f8167db5aec08bb69
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Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.

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