Autism spectrum disorder (ASD) is characterized 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, Caenorhabditis 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 utilize 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 into complex social behaviour.

中文翻译：

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秀丽隐杆线虫社会行为的 Neuroligin 依赖性为研究自闭症相关基因提供了一个模型

自闭症谱系障碍 (ASD) 的特征是包括社交行为在内的三种行为障碍。Neuroligin 是一种跨突触粘附分子，已成为表征自闭症神经非典型行为的行为特征的渗透遗传决定因素。然而，neuroligin 在社会回路中的功能以及遗传变异对该基因的影响尚不完全清楚。事实上，在旨在模拟自闭症的动物研究中，关于神经蛋白功能障碍在社会行为紊乱表达中的作用仍然存在争议。模式生物，秀丽隐杆线虫，提供了一个信息丰富的实验平台来研究遗传变异对社会行为的影响。在许多范式中，已经表明化学线索的生物间交流调节了秀丽隐杆线虫的社会行为。我们利用这种社会行为来研究自闭症相关遗传变异在研究领域标准的社会领域内的影响。我们已将神经配体确定为社会行为的重要调节剂，并将该基因对社会线索的识别和/或处理的重要性分开。我们还使用 CRISPR/Cas9 编辑了一个 RC 突变，该突变模拟了与自闭症相关的高度外显人类突变。携带这种突变的秀丽隐杆线虫表现了秀丽隐杆线虫的行为功能障碍Neuroligin 无效突变体，从而证实其在动物社会生物学调节中的重要性。这强调了定量行为和精确的基因干预可用于操纵蠕虫的离散社会回路，以进一步了解复杂的社会行为。