A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling.

ABSTRACT: The genetic etiology and underlying mechanism of autism spectrum disorder (ASD) remain elusive. SHANK family genes (SHANK1/2/3) are well known ASD-related genes. However, little is known about how SHANK missense mutations contribute to ASD. Here, we aimed to clarify the molecular mechanism of and the multilevel neuropathological features induced by Shank1 mutations in knock-in (KI) mice. In this study, by sequencing the SHANK1 gene in a cohort of 615 ASD patients and 503 controls, we identified an ASD-specific recurrent missense mutation, c.2621 G > A (p.R874H). This mutation demonstrated strong pathogenic potential in in vitro experiments, and we generated the corresponding Shank1 R882H-KI mice. Shank1 R882H-KI mice displayed core symptoms of ASD, namely, social disability and repetitive

SUBMITTER: Qin Y 

PROVIDER: S-EPMC9205781 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature