title: Decreased locomotor activity in mice expressing tTA under control of the CaMKII alpha promoter.
abstract: Transgenic mice in which the tetracycline transactivator (tTA) is driven by the forebrain-specific calcium-calmodulin-dependent kinase II alpha promoter (CaMKII alpha-tTA mice) are used to study the molecular genetics of many behaviors. These mice can be crossed with other transgenic mice carrying a transgene of interest coupled to the tetracycline-responsive promoter element to produce mice with forebrain-specific expression of the transgene under investigation. The value of using CaMKII alpha-tTA mice to study behavior, however, is dependent on the CaMKII alpha-tTA mice themselves lacking a behavioral phenotype with respect to the behaviors being studied. Here we present data that suggest CaMKII alpha-tTA mice have a behavioral phenotype distinct from that of their wild-type (WT) littermates. Most strikingly, we find that CaMKII alpha-tTA mice, both those with a C57BL/6NTac genetic background (B6-tTA) and those with a 129S6B6F1/Tac hybrid genetic background (F1-tTA), exhibit decreased locomotor activity compared with WT littermates that could be misinterpreted as altered anxiety-like behavior. Despite this impairment, neither B6-tTA nor F1-tTA mice perform differently than their WT littermates in two commonly used learning and memory paradigms - Pavlovian fear conditioning and Morris water maze. Additionally, we find data regarding motor coordination and balance to be mixed: B6-tTA mice, but not F1-tTA mice, exhibit impaired performance on the accelerating rotarod and both perform as well as their WT littermates on the balance beam.
authors.affiliation: Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109-2200, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: McKinney
authors.forename: J S
authors.initials: JS
authors.lastname: Schneider
authors.forename: G L
authors.initials: GL
authors.lastname: Schafer
authors.forename: J L
authors.initials: JL
authors.lastname: Lowing
authors.forename: S
authors.initials: S
authors.lastname: Mohan
authors.forename: M X
authors.initials: MX
authors.lastname: Zhao
authors.forename: M Y
authors.initials: MY
authors.lastname: Heng
authors.forename: R L
authors.initials: RL
authors.lastname: Albin
authors.forename: A F
authors.initials: AF
authors.lastname: Seasholtz
authors.forename: H
authors.initials: H
authors.lastname: Akil
authors.forename: G G
authors.initials: GG
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001007:Anxiety; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics*; D003624:Darkness; D005106:Exploratory Behavior; D008027:Light; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D013752:Tetracycline / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D015534:Trans-Activators; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D013752:Tetracycline