| First Author | Jaramillo TC | Year | 2020 |
| Journal | eNeuro | Volume | 7 |
| Issue | 3 | PubMed ID | 32327468 |
| Mgi Jnum | J:289177 | Mgi Id | MGI:6431169 |
| Doi | 10.1523/ENEURO.0332-19.2020 | Citation | Jaramillo TC, et al. (2020) Early restoration of Shank3 expression in Shank3 knockout mice prevents core ASD-like behavioural phenotypes. eNeuro :ENEURO.0332-19.2020 |
| abstractText | Several genes are associated with increased risk for ASD (Autism Spectrum Disorder), 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 SHANK3, a well-characterized gene encoding a postsynaptic scaffolding protein, are estimated to contribute to approximately 0.5% 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 Shank3 mutation can prevent the onset of ASD-like behaviors in a mouse model. Previously, we have demonstrated that mice deficient in Shank3 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 Shank3 mutant mice. With early genetic restoration of wild-type Shank3, 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 Shank3 are susceptible to early genetic correction of Shank3 mutations.Significance Statement Rare, de novo, single gene copy number variants and mutations are known causes of autism. The SHANK3 gene is among the most common and replicated genetic causes of autism. With the advent of gene therapy, interest is growing in understanding whether genetic animal models of autism can have their phenotypes ameliorated by genetic reversal. This study confirms that early genetic restoration of a Shank3 mutant mouse model can ameliorate behavioral symptoms with face validity for autism. |
