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International Journal of Alzheimer’s Disease
Volume 2012 (2012), Article ID 873270, 8 pages
http://dx.doi.org/10.1155/2012/873270
Review Article

Lessons from Tau-Deficient Mice

Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, The University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia

Received 21 March 2012; Accepted 19 April 2012

Academic Editor: Rakez Kayed

Copyright © 2012 Yazi D. Ke et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Both Alzheimer's disease (AD) and frontotemporal dementia (FTD) are characterized by the deposition of hyperphosphorylated forms of the microtubule-associated protein tau in neurons and/or glia. This unifying pathology led to the umbrella term “tauopathies” for these conditions, also emphasizing the central role of tau in AD and FTD. Generation of transgenic mouse models expressing human tau in the brain has contributed to the understanding of the pathomechanistic role of tau in disease. To reveal the physiological functions of tau in vivo, several knockout mouse strains with deletion of the tau-encoding MAPT gene have been established over the past decade, using different gene targeting constructs. Surprisingly, when initially introduced tau knockout mice presented with no overt phenotype or malformations. The number of publications using tau knockout mice has recently markedly increased, and both behavioural changes and motor deficits have been identified in aged mice of certain strains. Moreover, tau knockout mice have been instrumental in identifying novel functions of tau, both in cultured neurons and in vivo. Importantly, tau knockout mice have significantly contributed to the understanding of the pathophysiological interplay between Aβ and tau in AD. Here, we review the literature that involves tau knockout mice to summarize what we have learned so far from depleting tau in vivo.