CRISPR-mediated activation of autism gene Itgb3 restores cortical network excitability via mGluR5 signaling.

ABSTRACT: Many mutations in autism spectrum disorder (ASD) affect a single allele, indicating a key role for gene dosage in ASD susceptibility. Recently, haplo-insufficiency of ITGB3, the gene encoding the extracellular matrix receptor β3 integrin, was associated with ASD. Accordingly, Itgb3 knockout (KO) mice exhibit autism-like phenotypes. The pathophysiological mechanisms of Itgb3 remain, however, unknown, and the potential of targeting this gene for developing ASD therapies uninvestigated. By combining molecular, biochemical, imaging, and pharmacological analyses, we establish that Itgb3 haplo-insufficiency impairs cortical network excitability by promoting extra-synaptic over synaptic signaling of the metabotropic glutamate receptor mGluR5, which is similarly dysregu

SUBMITTER: Jaudon F 

PROVIDER: S-EPMC9382421 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature