A recent study published in PNAS has found that knocking out the Astrotactin 2 (ASTN2) gene leads to several hallmark behaviors of autism spectrum disorder (ASD) in mice. The researchers, from the Laboratory of Developmental Neurobiology at Rockefeller University, discovered how defects in the protein produced by the ASTN2 gene disrupted circuitry in the cerebellum in children with neurodevelopmental conditions.
The study found that mice lacking ASTN2 showed distinctly different behaviors compared to their wild-type nestmates. The knockout mice vocalized and socialized less, but were more hyperactive and repetitive in their behavior. These traits have parallels in people with ASD, including issues with language, social communication, hyperactivity, and repetitive movements.
The researchers also found structural and physiological changes in the cerebellum of the knockout mice. They detected a higher density of dendritic spines on Purkinje cells, which are large neurons responsible for processing sensory information. Additionally, they found a decrease in the number of immature dendritic spines (filopodia) and the volume of Bergmann glial fibers.
The study’s lead author, Michalina Hanzel, says that the findings have implications for our understanding of ASD. “It’s a big finding in the field of neuroscience,” she says. “It also underscores this emerging story that the cerebellum has cognitive functions that are quite independent of its motor functions.”
The researchers plan to study human cerebellar cells and cells with ASTN2 mutations donated by the family in the 2018 study. They hope to find parallel differences between mice and humans, which could provide insights into the biology of ASD.
This study is an important step towards understanding the complex genetic mechanisms underlying ASD. By examining the effects of knocking out individual genes, researchers can gain a deeper understanding of how these genes contribute to the development of ASD.
Source: https://medicalxpress.com/news/2024-08-key-gene-autistic-traits-mouse.html