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An investigation into the effect of the social environment on the phenotypes of mice lacking Nlgn3 and their wild-type littermates

Kalbassi, Shireene 2019. An investigation into the effect of the social environment on the phenotypes of mice lacking Nlgn3 and their wild-type littermates. PhD Thesis, Cardiff University.
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Abstract

The main focus of this thesis was to investigate if the social environment may be a factor leading to aberrant behavioural changes in the Nlgn3 knockout mouse, a model of autism spectrum disorder (ASD). Initial observations revealed that mixed genotype housed male Nlgn3 knockout mice and wild-type mice displayed deficits in their social behaviours and anxiety-related behaviours compared to male Nlgn3 knockout mice and wild-type mice in single genotype housed conditions. Selective re-expression of Nlgn3 in parvalbumin expressing cells in transgenic mice rescued their social behaviour and alleviated the phenotypes of their wild-type littermates, thus further indicating that the social behaviour of Nlgn3 knockout mice has a direct and measurable impact on their wild-type littermates’ behaviour. Additionally, the social environment was confirmed to alter the transcriptome profile of the striatum and the hippocampus, as assessed by RNA sequencing. Following this, the question of the sex-specific sensitivity to the social environment was assessed by studying female Nlgn3 knockout mice and their littermates. This revealed that the social environment is a factor influencing the behaviour of female Nlgn3 knockout and wild-type mice. Finally, the potential generalization of the findings to other models for ASD was addressed, by assessing if Neuroligin-3 interacts with other proteins that are known risk factors for ASD. Together, these results demonstrate that Nlgn3 knockout male and female mice show behavioural and physiological changes dependent on the social environment and that this is mediated by parvalbumin-expressing cells. Furthermore, the interaction of Neuroligin-3 with other ASD-related proteins suggest that other mouse models of ASD may also show this sensitivity to the social environment.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Biosciences
Uncontrolled Keywords: autism; mice; social parvalbumin
Date of First Compliant Deposit: 15 May 2019
Last Modified: 16 May 2019 09:21
URI: http://orca-mwe.cf.ac.uk/id/eprint/122538

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