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  • Mitchell et al., 2020

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

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Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model : a central role for gene-environment interactions. / Mitchell, Emma J; Thomson, David M; Openshaw, Rebecca L; Bristow, Greg C.; Dawson, Neil; Pratt, Judith A; Morris, Brian J.

In: Scientific Reports, Vol. 10, No. 1, 12303, 23.07.2020.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Mitchell, EJ, Thomson, DM, Openshaw, RL, Bristow, GC, Dawson, N, Pratt, JA & Morris, BJ 2020, 'Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions', Scientific Reports, vol. 10, no. 1, 12303. https://doi.org/10.1038/s41598-020-69130-8

APA

Mitchell, E. J., Thomson, D. M., Openshaw, R. L., Bristow, G. C., Dawson, N., Pratt, J. A., & Morris, B. J. (2020). Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions. Scientific Reports, 10(1), [12303]. https://doi.org/10.1038/s41598-020-69130-8

Vancouver

Mitchell EJ, Thomson DM, Openshaw RL, Bristow GC, Dawson N, Pratt JA et al. Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions. Scientific Reports. 2020 Jul 23;10(1). 12303. https://doi.org/10.1038/s41598-020-69130-8

Author

Mitchell, Emma J ; Thomson, David M ; Openshaw, Rebecca L ; Bristow, Greg C. ; Dawson, Neil ; Pratt, Judith A ; Morris, Brian J. / Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model : a central role for gene-environment interactions. In: Scientific Reports. 2020 ; Vol. 10, No. 1.

Bibtex

@article{a10763cf06ac41e2a792cb168af07ce7,
title = "Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions",
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.",
author = "Mitchell, {Emma J} and Thomson, {David M} and Openshaw, {Rebecca L} and Bristow, {Greg C.} and Neil Dawson and Pratt, {Judith A} and Morris, {Brian J}",
year = "2020",
month = jul,
day = "23",
doi = "10.1038/s41598-020-69130-8",
language = "English",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model

T2 - a central role for gene-environment interactions

AU - Mitchell, Emma J

AU - Thomson, David M

AU - Openshaw, Rebecca L

AU - Bristow, Greg C.

AU - Dawson, Neil

AU - Pratt, Judith A

AU - Morris, Brian J

PY - 2020/7/23

Y1 - 2020/7/23

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-020-69130-8

DO - 10.1038/s41598-020-69130-8

M3 - Journal article

C2 - 32704009

VL - 10

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12303

ER -