A hyper-activatable CAMK2A variant associated with intellectual disability causes exaggerated long-term potentiation and learning impairments.

ABSTRACT: Intellectual disability (ID) is a neurodevelopmental disorder (NDD) characterized by impairments in intellectual and adaptive functioning, and is highly co-morbid with other NDDs. Recently, de novo missense variants in the gene, CAMK2A, which encodes calcium/calmodulin-dependent protein kinase IIα (CaMKIIα), an abundant neuronal protein crucial for synaptic plasticity, learning and memory, have been implicated in ID. However, the causative impact of these mutations remains underexplored. In this study, we developed a heterozygous knock-in mouse model carrying the most prevalent ID-associated CAMK2A de novo missense variant, P212L, as a gain-of-function allele. The knock-in mice exhibited increased autophosphorylation of CaMKIIα, indicative of exuberant kinase activity, and consistently sho

SUBMITTER: Pan M 

PROVIDER: S-EPMC11947108 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature