Assessment of Autistic-like Behaviour of Mice Lacking ATRX in Forebrain Glutamatergic Neurons

Mutations in ATRX, which encodes a chromatin remodeling protein, have been identified in patients with autism and are associated with ATR-X syndrome, a genetic disorder characterized by cognitive deficits, developmental delays, and autistic-like behaviour. Despite the relationship between ATRX and autism, it is not yet known how mutations lead to autistic behaviour. To investigate this relationship, we generated two mouse models displaying distinct timing of Atrx inactivation in forebrain excitatory neurons. With these models, we performed behavioural paradigms to assess behaviour related to autism. Behavioural testing revealed that the conditional deletion of Atrx in differentiated forebrain neurons during embryogenesis leads to aggressive social behaviour, overgrooming stereotypies, and an exaggerated startle response in male mice. However, these autistic-like traits were not observed after a postnatal deletion of Atrx in forebrain neurons. We conclude that neuronal ATRX is required at early stages of forebrain development to suppress autistic-like behaviour in male mice.