Skip Navigation LinksHome > November 2011 - Volume 70 - Issue 11 > Gene Knockout of tau Expression Does Not Contribute to the P...
Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0b013e318235b471
Original Articles

Gene Knockout of tau Expression Does Not Contribute to the Pathogenesis of Prion Disease

Lawson, Victoria A. PhD; Klemm, Helen M. BSc; Welton, Jeremy M. BSc; Masters, Colin L. MD; Crouch, Peter PhD; Cappai, Roberto PhD; Ciccotosto, Giuseppe D. PhD

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Abstract

Prion diseases or transmissible spongiform encephalopathies are agroup of fatal and transmissible disorders affecting the central nervous system of humans and animals. The principal agent of prion disease transmission and pathogenesis is proposed to be an abnormalprotease-resistant isoform of the normal cellular prion protein. The microtubule-associated protein tau is elevated in patients with Creutzfeldt-Jakob disease. To determine whether tau expression contributesto prion disease pathogenesis, tau knockout and control wild-type mice were infected with the M1000 strain of mouse-adapted human prions. Immunohistochemical analysis for total tau expressionin prion-infected wild-type mice indicated tau aggregation in the cytoplasm of a subpopulation of neurons in regions associated with spongiform change. Western immunoblot analysis of brain homogenates revealed a decrease in total tau immunoreactivity and epitope-specific changes in tau phosphorylation. No significant difference in incubation period or other disease features were observed between tau knockout and wild-type mice with clinical prion disease. These results demonstrate that, in this model of prion disease, tau does not contribute to the pathogenesis of prion disease and that changes in the tau protein profile observed in mice with clinical prion disease occurs as a consequence of the prion-induced pathogenesis.

© 2011 American Association of Neuropathologists, Inc

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