KDM5A mutations identified in autism spectrum disorder using forward genetics.

ABSTRACT: Autism spectrum disorder (ASD) is a constellation of neurodevelopmental disorders with high phenotypic and genetic heterogeneity, complicating the discovery of causative genes. Through a forward genetics approach selecting for defective vocalization in mice, we identified Kdm5a as a candidate ASD gene. To validate our discovery, we generated a Kdm5a knockout mouse model (Kdm5a^-/-) and confirmed that inactivating Kdm5a disrupts vocalization. In addition, Kdm5a^-/- mice displayed repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis. Loss of KDM5A also resulted in dysregulation of the hippocampal transcriptome. To determine if KDM5A mutations cause ASD in humans, we screened whole

SUBMITTER: El Hayek L 

PROVIDER: S-EPMC7755391 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature