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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2014

Open Access 01-12-2014 | Research article

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

Authors: Peng Lei, Scott Ayton, Steve Moon, Qihao Zhang, Irene Volitakis, David I Finkelstein, Ashley I Bush

Published in: Molecular Neurodegeneration | Issue 1/2014

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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.
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Metadata
Title
Motor and cognitive deficits in aged tau knockout mice in two background strains
Authors
Peng Lei
Scott Ayton
Steve Moon
Qihao Zhang
Irene Volitakis
David I Finkelstein
Ashley I Bush
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2014
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-9-29

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