title: Effect size of memory deficits in mice with adult-onset P301L tau expression.
abstract: Transgenic mice expressing mutations in tau have yielded essential discoveries for Alzheimer's disease. One of the most commonly used tau mouse models is the tet-off Tg(tauP301L)4510 model that expresses P301L human tau driven by the calcium-calmodulin kinase IIα (CaMKIIα) promoter system. Tau expression in this model is regulatable, allowing for suppression of mutant tau expression until adulthood and prevention of possible developmental alterations resulting from P301L tau expression during development. Here, we compared the effect and sample sizes needed for three learning and memory tasks in mice with adult-onset P301L tau expression. Our findings indicate that the Incremental Repeated Acquisition (IRA) and trace fear conditioning tasks, neither of which have previously been published with these mice, were highly sensitive to P301L tau expression, whereas the Morris water maze, the most commonly used task with this model, was the least sensitive. Memory deficits were observed at a time when tau pathology was subtle and prior to readily detectable neuronal loss. Thus, we provide essential information (effect and sample sizes needed) for establishing experimental designs at a time point when memory deficits are likely to go undetected if inadequate sample sizes are used. Our work also suggests the tet-off Tg4510 model provides a way to avoid mutant tau expression during the perinatal and early postnatal stages, thereby preventing possible developmental alterations unrelated to Alzheimer's disease.
authors.affiliation: Department of Psychology, Behavioral Neuroscience, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Holly C
authors.initials: HC
authors.lastname: Hunsberger
authors.affiliation: Department of Psychology, Behavioral Neuroscience, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Carolyn C
authors.initials: CC
authors.lastname: Rudy
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Weitzner
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Psychology, Behavioral Neuroscience, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Tosto
authors.affiliation: Department of Psychology, Behavioral Neuroscience, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Knowlan
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Psychology, Behavioral Neuroscience, West Virginia University, Morgantown, WV 26506, USA; Center for Neuroscience, West Virginia University, Morgantown, WV 26506, USA; Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, WV 26506, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: Miranda.Reed@mail.wvu.edu.
authors.forename: Miranda N
authors.initials: MN
authors.lastname: Reed
mesh_terms: D017668:Age of Onset; D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D050882:CREB-Binding Protein / Q000378:metabolism; D003213:Conditioning, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005239:Fear / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology*; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000473:pathology; D009483:Neuropsychological Tests; D024801:Tauopathies / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse
keywords: Alzheimer's disease; Fear conditioning; Incremental repeated acquisition; Memory; Tau; Tg4510