Generation and behavior characterization of CaMKIIß knockout mice.

ABSTRACT

The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain, where it makes important contributions to synaptic organization and homeostasis, including playing an essential role in synaptic plasticity and memory. Four genes encode isoforms of CaMKII (α, ß, δ, γ), with CaMKIIα and CaMKIIß highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKIIα mutant mouse lines, have provided insight into the pivotal roles of CaMKIIα in brain plasticity and cognition. However, less is known about the CaMKIIß isoform. We report the development and extensive behavioral and phenotypic characterization of a CaMKIIß knockout (KO) mouse. The CaMKIIß KO mouse was found to be smaller at weaning, with an altered body mass composition. The CaMKIIß KO mouse showed ataxia, impaired forelimb grip strength, and deficits in the rotorod, balance beam and running wheel tasks. Interestingly, the CaMKIIß KO mouse exhibited reduced anxiety in the elevated plus maze and open field tests. The CaMKIIß KO mouse also showed cognitive impairment in the novel object recognition task. Our results provide a comprehensive behavioral characterization of mice deficient in the ß isoform of CaMKII. The neurologic phenotypes and the construction of the genotype suggest the utility of this KO mouse strain for future studies of CaMKIIß in brain structure, function and development.