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bioRxiv · 10.1101/2020.02.03.931592

Neuroligin dependence of social behaviour in C. elegans provides a model to investigate an autism associated gene

Rawsthorne, H.·Calahorro, F.·Feist, E.·Holden-Dye, L.·O'Connor, V.·Dillon, J.
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Abstract

Autism spectrum disorder (ASD) is characterised by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neuroligin in social circuitry and the impact of genetic variation to this gene is not fully understood. Indeed, in animal studies designed to model autism there remains controversy regarding the role of neuroligin dysfunction in the expression of disrupted social behaviours. The model organism, C. elegans, offers an informative experimental platform to investigate the impact of genetic variants on social behaviour. In a number of paradigms it has been shown that inter-organismal communication by chemical cues regulates C. elegans social behaviour. We utilise this social behaviour to investigate the effect of autism associated genetic variants within the social domain of the research domain criteria. We have identified neuroligin as an important regulator of social behaviour and segregate the importance of this gene to the recognition and/or processing of social cues. We also use CRISPR/Cas9 to edit an R-C mutation that mimics a highly penetrant human mutation associated with autism. C. elegans carrying this mutation phenocopy the behavioural dysfunction of a C. elegans neuroligin null mutant, thus confirming its significance in the regulation of animal social biology. This highlights that quantitative behaviour and precision genetic intervention can be used to manipulate discrete social circuits of the worm to provide further insight to complex social behaviour.

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Rawsthorne, H., Calahorro, F., Feist, E., Holden-Dye, L., O'Connor, V., Dillon, J.. 2020-02-04. Neuroligin dependence of social behaviour in C. elegans provides a model to investigate an autism associated gene. https://doi.org/10.1101/2020.02.03.931592

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