Genetic and environmental mouse models of autism reproduce the spectrum of the disease.

Researchers studied three different mouse models that mimic autism in animals. They found that all three models showed problems in a brain area called the cerebellum, which affects movement and coordination. The mice had walking difficulties that matched their social problems. Male mice were more affected than females, just like in human autism. This research suggests that movement problems in autism might be more important than previously thought.

This review examines three mouse models of autism spectrum disorder: valproic acid exposure, poly I:C infection, and Shank3 genetic mutation models. The authors report that all three models demonstrate behavioral, cellular, and molecular changes in the cerebellum, with motor and gait deficits correlating with social impairments and cerebellar Purkinje cell numbers. Male mice showed more severe symptoms than females across models, mirroring human autism patterns. The research highlights the cerebellum's role in connecting cognitive, social, and motor functions in autism, suggesting this brain region as a potential therapeutic target.

The findings support motor symptoms as underexplored aspects of autism pathophysiology.

Findings suggest motor symptoms warrant greater clinical attention in autism assessment and intervention. The cerebellum emerges as a potential therapeutic target. Sex differences should inform personalized treatment approaches. However, animal model findings require validation in human studies before clinical application.

This is a review of the authors' own work rather than a comprehensive systematic review. Sample sizes not reported. Limited to three specific animal models. Motor assessments may not translate directly to human autism presentations.

Genetic and environmental factors increase autism spectrum disorder (ASD) incidence, and this has led to the generation of corresponding animal models, with some showing strong construct and face validity. This short review focuses on results we have recently obtained with environmental and genetic mouse models of ASD and that are the valproic acid, the poly I:C and the Shank 3 models. This has allowed us to provide a comparative description of these widely used animal models providing an interesting perspective as to the pros and cons of each one of them, in our experimental settings. In these papers, we focused on motor and gait disorders which are currently not included in the diagnosis criteria, but which may provide new insights to ASD pathophysiology potentially leading to innovative therapies for a disease that currently has none.

In all these models, we reported behavioral, cellular and molecular alterations related to the cerebellum. Motor and gait deficits were observed to various degrees in animal models and, when strongly present, they were correlated to the severity of social deficits as well as to the number of cerebellar Purkinje cells. Additionally, we also reported that, like in humans, males are more severely affected than females in these ASD models. These findings, along with an increasing body of literature, open new hopes in the ASD field pointing to brain regions, such the cerebellum, that are at the crossroads between cognitive, social and motor deficits.

Targeting these brain regions and their underlying pathways and synaptic connections may prove of significant benefits.