Generation and Behavior Characterization of CaMKIIβ 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, 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.

Regulation of dendrite morphogenesis by extrinsic cues

“…These results define a catalytic function for CaMKIIβ in the mammalian brain that couples calcium signaling to cell-intrinsic pathways operating at the centrosome, thereby orchestrating dendrite pruning and retraction. Consistent with these findings, CaMKIIβ knockout mice display cognitive deficits and motor impairment [92], highlighting a non-redundant role for CaMKIIβ in neuronal development.…”

Nest‐building activity as a reproducible and long‐term stroke deficit test in a mouse model of stroke

“…These previous studies support the notion that striatal and hippocampal damage after mouse stroke may contribute to the nest‐building deficit. Nest‐building activity is virtually absent in mice deficient in calcium/calmodulin‐dependent protein kinase II (CaMKII) gene (Bachstetter et al., ). This may explain the nest‐building deficit after mouse MCAO because CaMKII activity is dramatically reduced in animal models of brain ischemia (Tang, Liu, Kuluz, & Hu, ).…”

“…Nest building is a natural behavior throughout the animal kingdom (Bachstetter et al., ). Primates such as extant strepsirrhines (lemurs and lorisoids) and hominid apes (gorillas, chimpanzees, and orangutans) build nests for both sleeping and also for raising families (Stewart, Pruetz, & Hansell, ; Stewart, ; van Casteren et al., ).…”

“…Small rodents build nests for bed and shelter. Nest‐building behavior in animals may be similar to preparing bed and maintaining houses in humans (Lin, Chen, Kuang, Wang, & Tsien, ; Bachstetter et al., ). Normal nest‐building activity also indicates an animal's well‐being and, perhaps most importantly, is performed spontaneously in the home cage without enforcement by investigators (Jirkof, ).…”

Determination of dibutyl phthalate neurobehavioral toxicity in mice

“…Resistance force of the forelimbs was calculated automatically by the apparatus. The test was repeated 3 times for each animal and the maximum force (gram) was reported as the final grip strength (Bachstetter et al, 2014).…”