Abstract
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a key modulator of excitatory synaptic transmission, gene expression, learning and memory. Mutations in the CAMK2A gene, which encodes CaMKIIα and is highly expressed in multiple regions in the forebrain, have been recently linked to neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Our lab generated and characterized a knock-in (KI) mutant mouse with a glutamate-183 to valine (E183V) CaMKIIα mutation detected in several children diagnosed with ASD or ID. The E183V mutation reduces CaMKIIα activity and expression levels but the contributions of these two changes to the ASD-related behavioral phenotypes of these mice are unclear. Therefore, we performed side-by-side comparisons of the behavioral phenotypes of CaMKIIα E183V-KI mice with two other mutant mouse lines with either a complete loss of CaMKIIα expression (CaMKIIα Null mice) or reduced kinase activity (due to a threonine-286 to alanine mutation that abrogates autophosphorylation at this site) with no significant change in expression levels (CaMKIIα T286A-KI mice). In all three lines, homozygous mutant mice displayed increased stereotypic jumping behavior and hyperactivity, without alterations in anxiety or social interactions. Interestingly, homozygous mutant mice in all three lines also displayed a substantial reduction in tactile sensitivity using the Von Frey filament test. Together, these data suggest that reductions of either CaMKIIα expression or activity in mice disrupted normal motor and sensory functions.
Competing Interest Statement
The authors have declared no competing interest.