Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions

Mitchell, E. J., Thomson, D. M., Openshaw, R. L. , Bristow, G. C., Dawson, N., Pratt, J. A. and Morris, B. (2020) Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions. Scientific Reports, 10, 12303. (doi: 10.1038/s41598-020-69130-8) (PMID:32704009) (PMCID:PMC7378168)

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Abstract

There are no current treatments for autism, despite its high prevalence. Deletions of chromosome 16p11.2 dramatically increase risk for autism, suggesting that mice with an equivalent genetic rearrangement may offer a valuable model for the testing of novel classes of therapeutic drug. 16p11.2 deletion (16p11.2 DEL) mice and wild-type controls were assessed using an ethological approach, with 24 h monitoring of activity and social interaction of groups of mice in a home-cage environment. The ability of the excitation/inhibition modulator N-acetyl cysteine (NAC) and the 5-HT1B/1D/1F receptor agonist eletriptan to normalise the behavioural deficits observed was tested. 16p11.2 DEL mice exhibited largely normal behaviours, but, following the stress of an injection, showed hyperlocomotion, reduced sociability, and a strong anxiolytic phenotype. The hyperactivity and reduced sociability, but not the suppressed anxiety, were effectively attenuated by both NAC and eletriptan. The data suggest that 16p11.2 DEL mice show an autism-relevant phenotype that becomes overt after an acute stressor, emphasising the importance of gene-environmental interactions in phenotypic analysis. Further, they add to an emerging view that NAC, or 5-HT1B/1D/1F receptor agonist treatment, may be a promising strategy for further investigation as a future treatment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Openshaw, Rebecca Louise and Pratt, Dr Judith and Morris, Professor Brian
Authors: Mitchell, E. J., Thomson, D. M., Openshaw, R. L., Bristow, G. C., Dawson, N., Pratt, J. A., and Morris, B.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
Copyright Holders:Copyright © The Author(s) 2020
First Published:First published in Scientific Reports 10:12303
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172418Characterising mice syntenic for human 16p11.2 in relation to schizophrenia and autism. ID 13267Brian MorrisMedical Research Council (MRC)MR/N012704/1NP - Centre for Neuroscience