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)
|
Text
220045.pdf - Published Version Available under License Creative Commons Attribution. 2MB |
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 Research |
| 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 |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information