Single gene linked to autism affects behaviour in mice

Deletion of a specific gene in mice leads to behaviours and brain changes characteristic of autism.

Autism spectrum disorder (ASD) is a developmental disorder characterised by challenges with social interaction, communication and repetitive behaviours. More than 70 genes have been linked to ASD, and now a study in mice has pointed to a critical role for one of these genes – the ASTN2 gene – in both cerebellar structure and function. The cerebellum is crucial in motor learning and cognitive functions and is known to be altered in people in ASD.

Professor Mary Hatten from Rockefeller University in New York and head of the laboratory that conducted the study, said: 'It's a big finding in the field of neuroscience.... It also underscores this emerging story that the cerebellum has cognitive functions that are quite independent of its motor functions.'

In the study, published in Proceedings of the National Academy of Sciences, researchers created a genetically altered mouse that does not express the Astn2 gene. They found that infant and adult mice without Astn2 had behaviours that have parallels with people with ASD, including communication issues and an increase in hyperactivity and repetitive actions. The mice without Astn2 also had corresponding structural and physiological changes in the cerebellum. These changes were most pronounced in distinct cerebellar subregions associated with the ASD-like behaviours presented by the mice.

'The differences are quite subtle, but they are clearly affecting how the mice are behaving,' said Professor Hatten. 'The changes are probably altering the communication between the cerebellum and the rest of the brain.'

Next, the researchers plan to investigate human cerebellar cells developed from stem cells, as well as human cells with ASTN2 mutations, to see if their findings in mice can be replicated in human cells.

Professor Hatten added: 'We also want to look at the detailed biology of other genes that are associated with autism. There are dozens of them, but there's no agreed-upon commonality that binds them together. We're very excited that we've been able to show in detail what ASTN2 does, but there are a lot more genes to investigate.'