title: 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.
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Bachstetter
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Webster
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Tao
authors.initials: T
authors.lastname: Tu
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Goulding
authors.affiliation: Laboratoire d'Innovation Thérapeutique, University of Strasbourg, Strasbourg, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Haiech
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: D Martin
authors.initials: DM
authors.lastname: Watterson
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America; Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Eldik
mesh_terms: D000818:Animals; D001007:Anxiety / Q000201:enzymology; D001259:Ataxia / Q000201:enzymology; D001823:Body Composition; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics* / Q000378:metabolism; D003072:Cognition Disorders / Q000201:enzymology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053580:Muscle Strength; D009425:Nesting Behavior; D046709:Pattern Recognition, Physiological; D045442:Rotarod Performance Test; D015430:Weight Gain
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2