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Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.
PLoS One. 2013; 8(6):e67114.Plos

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 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.

METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23840597

Citation

Grayton, Hannah Mary, et al. "Altered Social Behaviours in Neurexin 1α Knockout Mice Resemble Core Symptoms in Neurodevelopmental Disorders." PloS One, vol. 8, no. 6, 2013, pp. e67114.
Grayton HM, Missler M, Collier DA, et al. Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders. PLoS ONE. 2013;8(6):e67114.
Grayton, H. M., Missler, M., Collier, D. A., & Fernandes, C. (2013). Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders. PloS One, 8(6), e67114. https://doi.org/10.1371/journal.pone.0067114
Grayton HM, et al. Altered Social Behaviours in Neurexin 1α Knockout Mice Resemble Core Symptoms in Neurodevelopmental Disorders. PLoS ONE. 2013;8(6):e67114. PubMed PMID: 23840597.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders. AU - Grayton,Hannah Mary, AU - Missler,Markus, AU - Collier,David Andrew, AU - Fernandes,Cathy, Y1 - 2013/06/28/ PY - 2013/03/25/received PY - 2013/05/16/accepted PY - 2013/7/11/entrez PY - 2013/7/11/pubmed PY - 2014/1/22/medline SP - e67114 EP - e67114 JF - PloS one JO - PLoS ONE VL - 8 IS - 6 N2 - 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 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23840597/Altered_social_behaviours_in_neurexin_1α_knockout_mice_resemble_core_symptoms_in_neurodevelopmental_disorders_ L2 - http://dx.plos.org/10.1371/journal.pone.0067114 DB - PRIME DP - Unbound Medicine ER -