Journal Article

Altered Social Behaviours in Neurexin 1α Knockout Mice Resemble Core Symptoms in Neurodevelopmental Disorders

Grayton, Hannah Mary, Collier, David Andrew, Fernandes, Cathy, Missler, Markus

2013

Overview

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. 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). 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aggression / Aggressive behavior / Animals / Anxiety - genetics / Autism / Behavior / Biology / Copy number / Defects / Developmental Disabilities - genetics / Developmental Disabilities - psychology / Disease Models, Animal / Disorders / Female / Genes / Genetics / Glycoproteins - genetics / Glycoproteins - metabolism / Humans / Intellectual disabilities / Locomotor activity / Male / Medicine / Memory / Memory Disorders - genetics / Memory Disorders - psychology / Memory, Episodic / Mental disorders / Mental Disorders - genetics / Mental Disorders - psychology / Mice / Mice, 129 Strain / Mice, Inbred C57BL / Mice, Knockout / Motor Activity / Nesting Behavior / Neurobiology / Neurodevelopmental disorders / Neuropeptides - genetics / Neuropeptides - metabolism / Neurosciences / Psychiatry / Rodents / Schizophrenia / Social Behavior / Synaptic transmission