Tracking prions: the neurografting approach |
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Authors: | A Aguzzi T Blättler M A Klein A J Räber I Hegyi R Frigg S Brandner C Weissmann |
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Institution: | (1) Institute of Neuropathology (Dept. of Pathology), University of Zürich, CH-8091 Zürich (Switzerland), CH;(2) Institute of Molecular Biology, University of Zürich, CH-8091 Zürich (Switzerland), CH |
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Abstract: | The physical nature of the agent that causes transmissible spongiform encephalopathies (the 'prion'), is the subject of passionate
controversy. Investigation of it has benefited tremendously from the use of transgenic and knockout technologies. However,
prion diseases present several other enigmas, including the mechanism of brain damage and how the affinity of the agent for
the central nervous system is controlled. Here we show that such questions can be effectively addressed in transgenic and
knockout systems, and that pathogenesis may be clarified even before we can be certain about the nature of the infectious
agent. Availability of mice overexpressing the Prnp gene (which encodes the normal prion protein) and Prnp knockout mice allows for selective reconstitution experiments aimed at expressing PrP in specific portions of the brain or
in selected populations of hemato- and lymphopoietic origin. We summarize how such studies can offer insights into how prions
administered to peripheral sites can gain access to central nervous tissue, and into the molecular requirements for spongiform
brain damage. |
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Keywords: | , Prion diseases, neurografts, BSE, scrapie, transgenic mice, knockout mice, spongiform encephalopathies, |
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