title: The molecular, temporal and region-specific requirements of the beta isoform of Calcium/Calmodulin-dependent protein kinase type 2 (CAMK2B) in mouse locomotion.
abstract: Genetic approaches using temporal and brain region-specific restricted gene deletions have provided a wealth of insight in the brain regions and temporal aspects underlying spatial and associative learning. However, for locomotion such extensive studies are still scarce. Previous studies demonstrated that Camk2b(-/-) mice, which lack the β isoform of Calcium/Calmodulin-dependent protein kinase 2 (CAMK2B), show very severe locomotion deficits. However, where these locomotion deficits originate is unknown. Here we made use of novel Camk2b mutants (Camk2b(f/f) and Camk2b(T287A)), to explore the molecular, temporal and brain region-specific requirements of CAMK2B for locomotion. At the molecular level we found that normal locomotion requires Calcium/Calmodulin mediated activation of CAMK2B, but CAMK2B autonomous activity is largely dispensable. At a systems level, we found that global deletion of Camk2b in the adult mouse causes only mild locomotion deficits, suggesting that the severe locomotion deficits of Camk2b(-/-) mice are largely of developmental origin. However, early onset deletion of Camk2b in cerebellum, striatum or forebrain did not recapitulate the locomotion deficits, suggesting that these deficits cannot be attributed to a single brain area. Taken together, these results provide the first insights into the molecular, temporal and region-specific role of CAMK2B in locomotion.
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Kool
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Jolet E
authors.initials: JE
authors.lastname: van de Bree
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Bodde
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Ype
authors.initials: Y
authors.lastname: Elgersma
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.|ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Geeske M
authors.initials: GM
authors.lastname: van Woerden
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001931:Brain Mapping; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000172:deficiency / Q000235:genetics*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D016548:Prosencephalon / Q000378:metabolism / Q000503:physiopathology; D045442:Rotarod Performance Test; D065853:Spatial Learning / Q000502:physiology*
chemical_list: D002147:Calmodulin; D007527:Isoenzymes; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517672:Camk2b protein, mouse; D002118:Calcium