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Autism is characterized by atypical social communication and stereotyped behaviors. We observed decreased locomotor activity, increased stereotyped self-grooming and modification of socio-sexual interaction compared to wild-type littermates. DEGs were identified mainly in the striatum and were associated with synaptic transmission e. Downregulated and upregulated genes were enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 D1-MSN and the dopamine 2 receptor D2-MSN , respectively.

Altogether, these results indicate altered gene expression in the striatum of Shank3 -deficient mice and strongly suggest, for the first time, that the excessive self-grooming of these mice is related to an imbalance in the striatal striosome and matrix compartments.

Autism is a neurodevelopmental condition characterized by atypical social communication and interactions associated with stereotyped behaviors and restricted interests.

More than genes have been robustly associated with autism pointing at biological pathways such as chromatin remodeling, protein translation and synaptic function Leblond et al. Among these genes, SHANK3 SH3 and multiple ankyrin repeat domain 3 codes for a scaffolding protein located at the postsynaptic density PSD of glutamatergic synapses where it interacts with other scaffolding proteins, cytoskeletal proteins, glutamate receptors and signaling molecules Monteiro and Feng, Through the use of multiple intragenic promoters and alternative splicing, several SHANK3 protein isoforms are differentially expressed according to developmental stage or brain region Wang et al.