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Clay Heighten and Debra Caudy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["eNeuro"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several genes are associated with increased risk for autism spectrum disorder (ASD), neurodevelopmental disorders that present with repetitive movements and restricted interests along with deficits in social interaction\/communication. While genetic alterations associated with ASD are present early in life, ASD-like behaviors are difficult to detect in early infancy. This raises the issue of whether reversal of an ASD-associated genetic alteration early in life can prevent the onset of ASD-like behaviors. Genetic alterations of<jats:italic>SHANK3<\/jats:italic>, a well-characterized gene encoding a postsynaptic scaffolding protein, are estimated to contribute to \u223c0.5% of ASD and remain one of the more replicated and well-characterized genetic defects in ASD. Here, we investigate whether early genetic reversal of a<jats:italic>Shank3<\/jats:italic>mutation can prevent the onset of ASD-like behaviors in a mouse model. Previously, we have demonstrated that mice deficient in<jats:italic>Shank3<\/jats:italic>display a wide range of behavioral abnormalities such as repetitive grooming, social deficits, anxiety, and motor abnormalities. In this study, we replicate many of these behaviors in<jats:italic>Shank3<\/jats:italic>mutant mice. With early genetic restoration of wild-type (WT)<jats:italic>Shank3<\/jats:italic>, we rescue behaviors including repetitive grooming and social, locomotor, and rearing deficits. Our findings support the idea that the underlying mechanisms involving ASD behaviors in mice deficient in<jats:italic>Shank3<\/jats:italic>are susceptible to early genetic correction of<jats:italic>Shank3<\/jats:italic>mutations.<\/jats:p>","DOI":"10.1523\/eneuro.0332-19.2020","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T21:45:16Z","timestamp":1587678316000},"page":"ENEURO.0332-19.2020","source":"Crossref","is-referenced-by-count":43,"title":["Early Restoration of<i>Shank3<\/i>Expression in<i>Shank3<\/i>Knock-Out Mice Prevents Core ASD-Like Behavioral Phenotypes"],"prefix":"10.1523","volume":"7","author":[{"given":"Thomas C.","family":"Jaramillo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy 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