Contribution of cerebellar CNTNAP2 to autism in a mouse model

Autism spectrum disorders represent a complex set of neurodevelopmental disorders that involve a combination of many different genes and environmental factors and affect multiple parts of the brain. The molecular and cellular mechanisms that lead to autism remain elusive.

Esther Becker and her colleagues at the University of Oxford in the U.K. plan to investigate whether certain genes that have been linked to autism play a role in the development of the cerebellum. The cerebellum has long been recognized for its function in motor control and learning, and as it is also implicated in higher cognitive functions, it might be important in autism. Becker and her team have identified autism-related genes that are highly expressed and functional during the development of the cerebellum. They plan to use mouse models of the disorder to explore whether specific expression of these genes in the cerebellum contributes to autism.

For their pilot project, Becker’s team plans to use mice lacking the gene that encodes contactin-associated protein-like 2 (CNTNAP2). These mice show three core behaviors of autism: repetitive behavior, and deficits in sociability and communication. In normal development, CNTNAP2 is highly expressed in the brain, including the cerebellum. The investigators plan to restore CNTNAP2 expression in the model mice specifically in the cerebellum during development, and then test whether this alleviates any autism-like behaviors in the mice. The results of this study may help to unravel the molecular and anatomical basis of autism and improve our understanding of the disease-causing mechanisms underlying the disorder.