title: Motor and cognitive deficits in aged tau knockout mice in two background strains.
abstract: BACKGROUND
  We recently reported that Parkinsonian and dementia phenotypes emerge between 7-12 months of age in tau-/- mice on a Bl6/129sv mixed background. These observations were partially replicated by another group using pure Bl6 background tau-/- mice, but notably they did not observe a cognitive phenotype. A third group using Bl6 background tau-/- mice found cognitive impairment at 20-months of age.
  
  
  RESULTS
  To reconcile the observations, here we considered the genetic, dietary and environmental variables in both studies, and performed an extended set of behavioral studies on 12-month old tau+/+, tau+/-, and tau-/- mice comparing Bl6/129sv to Bl6 backgrounds. We found that tau-/- in both backgrounds exhibited reduced tyrosine hydroxylase-positive nigral neuron and impaired motor function in all assays used, which was ameliorated by oral treatment with L-DOPA, and not confounded by changes in body weight. Tau-/- in the C57BL6/SV129 background exhibited deficits in the Y-maze cognition task, but the mice on the Bl6 background did not.
  
  
  CONCLUSIONS
  These results validate our previous report on the neurodegenerative phenotypes of aged tau-/- mice, and show that genetic background may impact the extent of cognitive impairment in these mice. Therefore excessive lowering of tau should be avoided in therapeutic strategies for AD.
authors.forename: Peng
authors.initials: P
authors.lastname: Lei
authors.forename: Scott
authors.initials: S
authors.lastname: Ayton
authors.forename: Steve
authors.initials: S
authors.lastname: Moon
authors.forename: Qihao
authors.initials: Q
authors.lastname: Zhang
authors.forename: Irene
authors.initials: I
authors.lastname: Volitakis
authors.forename: David I
authors.initials: DI
authors.lastname: Finkelstein
authors.affiliation: Oxidation Biology Unit, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia. ashley.bush@florey.edu.au.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
mesh_terms: D000375:Aging; D000818:Animals; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000235:genetics*; D004032:Diet; D004195:Disease Models, Animal; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics*; D010641:Phenotype; D013378:Substantia Nigra / Q000473:pathology; D016875:tau Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: D016875:tau Proteins