Modeling complex autistic-like behavior in mice and impact of obesity induced during pregnancy – ASDMOD

Autism spectrum disorder (ASD) is a frequent neurodevelopmental disease, whose diagnosis is based exclusively on behavioral criteria: i) social interaction deficits and ii) restricted, repetitive and stereotyped patterns of behavior, interests and activities. The etiology of ASD is multifactorial and many risk factors, including genetics and environment have been associated with increased risk of offspring with ASD. Gestational weight gain (GWG) is one critical factor of risk and affects >30% of women. We developed several mouse models that we tested using classical devices to investigate the impact of these risk factors, separately, on the core behavioral domains of ASD. These tests are restricted to single actions and do not allow studying the complex behavior of a cohort of mice all over the life, specifically in infancy. To overcome these restrictions, we built an automated video processing and behavior analysis systems, which allows unlimited observation duration and a high accuracy of tracking, using more than two mice in an open space. Our main objective is to improve the imaging and analysis capacities of this system. These improvements will allow us to i) model behaviours in ASD mouse models by performing a non-invasive, longitudinal and blind behavioral study of genetic and environmental mouse models of ASD; ii) investigate the impact of GWG on the offspring behaviors on new genetic mouse models combining genetic and environmental risks.
The project builds-up around three aims: 1) the setup of new powerful tools available to the whole scientific community to analyze a large panel autistic behaviors, observing freely moving mice, at adulthood but also during infancy and adolescence; 2) analysis of complex autistic behaviors to define the “core-symptoms” of autism present in genetic and environmental models as well as the behaviors specific to each model; 3) to measure the impact of a GWG, a frequent environmental factor, on” genetic susceptibility”.