Generation and Behavior Characterization of CaMKIIβ Knockout Mice

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 (alpha, beta, delta, gamma), with CaMKII alpha and CaMKII beta highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKII alpha mutant mouse lines, have provided insight into the pivotal roles of CaMKII alpha in brain plasticity and cognition. However, less is known about the CaMKII beta isoform. We report the development and extensive behavioral and phenotypic characterization of a CaMKII beta knockout (KO) mouse. The CaMKII beta KO mouse was found to be smaller at weaning, with an altered body mass composition. The CaMKII beta KO mouse showed ataxia, impaired forelimb grip strength, and deficits in the rotorod, balance beam and running wheel tasks. Interestingly, the CaMKII beta KO mouse exhibited reduced anxiety in the elevated plus maze and open field tests. The CaMKII beta KO mouse also showed cognitive impairment in the novel object recognition task. Our results provide a comprehensive behavioral characterization of mice deficient in the beta isoform of CaMKII. The neurologic phenotypes and the construction of the genotype suggest the utility of this KO mouse strain for future studies of CaMKII beta in brain structure, function and development.