Autism-like atypical face processing in <i>Shank3</i> mutant dogs.

Yuan, Siqi; Pang, Chenyu; Wu, Liang; Yi, Li; Guo, Kun; Jiang, Yong-Hui; Zhang, Yong Q; Han, Shihui · Sci Adv · 2025

basic_science · Level V

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Abstract

Atypical face processing is a neurocognitive basis of social deficits in autism spectrum disorder (ASD) and a candidate cognitive marker for the disease. Although hundreds of risk genes have been identified in ASD, it remains unclear whether mutations in a specific gene may cause ASD-like atypical face processing. Dogs have acquired exquisite face processing abilities during domestication and may serve as an effective animal model for studying genetic associations of ASD-like atypical face processing. Here, we showed that dogs with <i>Shank3</i> mutations exhibited behavioral and attentional avoidance of faces, contrasting with wild-type controls. Moreover, neural responses specific to faces (versus objects) recorded from the electrodes over the temporal cortex were significantly decreased and delayed in <i>Shank3</i> mutants compared to wild-type controls. Cortical responses in the frontal/parietal region underlying categorization of faces by species/breeds were reduced in <i>Shank3</i> mutants. Our findings of atypical face processing in dogs with <i>Shank3</i> mutations provide a useful animal model for studying ASD mechanisms and treatments.

Medical subject headings