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Haploinsufficiency of the SHANK3 gene is the primary cause of Phelan-McDermid syndrome (PMS), a severe neurodevelopmental disorder with intellectual disability and autism spectrum disorder. We previously reported that founder SHANK3 macaques had behaviors reminiscent of some aspects of PMS. However, insights into behavioral, physiological, and cognitive changes were limited due to the small cohort and mosaicism. We therefore generated a larger, F1 generation of heterozygous SHANK3 macaques to conduct more thorough studies. We found sleep disturbances, diminished exploration, atypical social interactions, stereotypical behaviors, and altered brain functional connectivity in SHANK3 macaques. Electroencephalogram recordings revealed a markedly diminished response to auditory stimulation. Cognitively, SHANK3 monkeys did not show major deficits in working memory tests but exhibited an impaired ability to learn and execute a paired-association memory task. We further developed a multi-task array to systemically evaluate autism-related phenotypes, which revealed the heterogeneity of phenotypes and established potential biomarkers for testing therapeutics.