LONGITUDINAL BEHAVIORAL PROFILING OF MNK1 AND NLGN3 KNOCKOUT MICE USING AUTOMATED HOME-CAGE TRACKING

Autism spectrum disorders (ASD) are highly heritable neurodevelopmental conditions associated with various health and social challenges. There is a considerable heterogeneity in autism characteristics, their developmental trajectories, underlying molecular mechanisms, and genetic architecture, and this variability hinders the identification of new biomarkers or treatment targets. One approach to overcome this challenge lies in breaking down autism heterogeneity into biologically meaningful subgroups. However, how to best establish these subgroups remains unclear. Here, we investigate whether subgrouping animals based on their shared behavioral characteristics could reveal underlying convergent molecular mechanisms. In the first step, this approach involves deep behavioral phenotyping using the Live Mouse Tracker, an integrated system that enables tracking of a group of animals in a home cage-like environment over a prolonged period of time to reveal stably expressed changes in behavior. We have started with the behavioral characterization of two lines - Neuroligin3 knockout and MNK1 knockout, previously shown to present differences in social behavior. We tracked animals at two timepoints, as juveniles and adults, to observe neurodevelopmental trajectories across multiple behavioral domains, including individual behavioral patterns and social interactions. Additionally, the phenotyping was complemented by the Open Field and Novel Object Recognition tests to provide comprehensive behavioral profiling with a broad relevance to neurodevelopmental conditions. This study provides insights into how autism-associated behavioral differences present over time and lays a foundation for expanding the behavioral and molecular characterization to additional autism models.