Dataset Information

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

ABSTRACT:

Background

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 1? (Nrxn1?) 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.

Methods

We performed a detailed investigation of the behavioural effects of Nrxn1? 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 Nrxn1? KO male and female mice were tested in a battery of behavioural tests (n?=?9-16 per genotype, per sex).

Results

In homozygous Nrxn1? KO mice, we observed altered social approach, reduced social investigation, and reduced locomotor activity in novel environments. In addition, male Nrxn1? KO mice demonstrated an increase in aggressive behaviours.

Conclusions

These are the first experimental data that associate a deletion of Nrxn1? 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 Nrxn1? KO mice are a useful model of human neurodevelopmental disorder.

SUBMITTER: Grayton HM

PROVIDER: S-EPMC3696036 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

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

Grayton Hannah Mary HM Missler Markus M Collier David Andrew DA Fernandes Cathy C

PloS one 20130628 6

<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 ...[more]

PMID: 23840597

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