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, β, δ, γ), with CaMKIIα and CaMKIIβ 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 CaMKIIβ isoform. We report the development and extensive behavioral and phenotypic characterization of a CaMKIIβ knockout (KO) mouse. The CaMKIIβ KO mouse was found to be smaller at weaning, with an altered body mass composition. The CaMKIIβ KO mouse showed ataxia, impaired forelimb grip strength, and deficits in the rotorod, balance beam and running wheel tasks. Interestingly, the CaMKIIβ KO mouse exhibited reduced anxiety in the elevated plus maze and open field tests. The CaMKIIβ KO mouse also showed cognitive impairment in the novel object recognition task. Our results provide a comprehensive behavioral characterization of mice deficient in the β isoform of CaMKII. The neurologic phenotypes and the construction of the genotype suggest the utility of this KO mouse strain for future studies of CaMKIIβ in brain structure, function and development.
Highlights
The calcium/calmodulin-dependent protein kinase II (CaMKII) family is key to transducing calcium signals into biological responses, especially in the central nervous system (CNS)
Generation of CaMKIIb KO mice As discussed in Methods, the CaMKIIb KO mouse line was generated at the MCI/ICS in Illkirch, France
Matings between heterozygotes generated wild-type (+/+), heterozygotes (+/2), and CaMKIIb KO (2/2) mice at a ratio of 30%, 54%, and 16% respectively for 293 mice born over a two year period
Summary
The calcium/calmodulin-dependent protein kinase II (CaMKII) family is key to transducing calcium signals into biological responses, especially in the central nervous system (CNS). CaMKIIa and CaMKIIb are both expressed at high levels in the hippocampus, where the role of the kinase in hippocampal long-term potentiation (LTP) is well described [4,5]). The a and b isoforms of CaMKII have been reported to have independent but essential functions in maintaining LTP [1,2,5]. CaMKIIb may affect synaptic function by altering the size and shape of the dendritic spines [6,7,8], or by localizing CaMKIIa to the dendritic spines [9]
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