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Investigation of social olfaction in a Neuroligin 3 Knockout mouse model

Cross, Ellen 2019. Investigation of social olfaction in a Neuroligin 3 Knockout mouse model. PhD Thesis, Cardiff University.
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Abstract

Mouse models contribute a lot to our understanding of human illness by allowing assessment of the effect of both genes and environment which can be used to answer important questions. Autism spectrum disorder (ASD) is a developmental disorder that does not have one single cause but can be due to a number of different causes. This ranges from single gene de novo mutations to an accumulation of mutations and with the addition of environmental effects ASD is a challenging disorder to understand. One of the genes associated with ASD is the NLGN3, an X-linked gene which encodes the protein Neuroligin 3. Neuroligin 3 forms a cell adhesion molecule found in the synapses of neurons and its main function is maintaining the stability of synapses. Neuroligin 3 knockout (Nlgn3y/-) mice have been studied for behavioural modifications and it was identified that Nlgn3y/- mice have a deficit in social memory. One of the main symptoms of ASD is deficits in social communication so this phenotype is worth exploring. As social odour production and detection is an important factor in social communication in mice we decided to pursue the social memory deficit of Nlgn3y/- mice in this context. I identified reduced interest for social cues and altered discrimination behaviour in Nlgn3y/- mice. Also an environmental effect where the genetics of the mice in a home environment also affect reactions to social cues. Both Neuroligin 3 knockout and housing affected cFos signal in discrete brain regions in response to a particular scent cue known as major urinary protein 20 (MUP20), particularly in the dentate gyrus. Neuroligin-3 was identified in the Vomeronasal organ (VNO), which is an olfactory tissue, however the role that this protein plays in VNO function has yet to be identified. These findings suggests that NLGN3 is a gene of importance to the social behaviour of mice and could contribute to social memory phenotypes identified in Nlgn3y/- mice.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: AOB: Accessory olfactory bulb ASD: Autism spectrum disorder HMW: High molecular weight IP: Immunoprecipitation LMW: Low molecular weight MGH: Mixed genotype housed MOB: Main olfactory bulb MOE: Main olfactory epithelium MUPs: Major urinary proteins OMP: Olfactory Marker protein SGH: Single genotype housed V1R: Vomeronasal receptor type 1 V2R: Vomeronasal receptor type 2 VNO: Vomeronasal organ
Funders: Wellcome Trust
Date of First Compliant Deposit: 10 July 2019
Last Modified: 18 Jul 2019 14:26
URI: http://orca-mwe.cf.ac.uk/id/eprint/124009

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