Motor and cognitive deficits in aged tau knockout mice in two background strains

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.