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Neuroinvasion of prions: insights from mouse models

Published online by Cambridge University Press:  10 January 2001

Sebastian Brandner*
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Michael A. Klein
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Rico Frigg
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Valdimir Pekarik
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Petra Parizek
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Alex Raeber
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Markus Glatzel
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Petra Schwarz
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Thomas Rulicke
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Charles Weissmann
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
Adriano Aguzzi
Affiliation:
Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, University Hospital, 8091 Zurich, Switzerland
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Abstract

The prion was defined by Stanley B. Prusiner as the infectious agent that causes transmissible spongiform encephalopathies. A pathological protein accumulating in the brain of scrapie-infected hamsters was isolated in 1982 and termed prion protein (PrPSc). Its cognate gene Prnp was identified more than a decade ago by Charles Weissmann, and shown to encode the host protein PrPC. Since the latter discovery, transgenic mice have contributed many important insights into the field of prion biology, including the understanding of the molecular basis of the species barrier for prions. By disrupting the Prnp gene, it was shown that an organism that lacks PrPC is resistant to infection by prions. Introduction of mutant PrP genes into PrP-deficient mice was used to investigate the structure-activity relationship of the PrP gene with regard to scrapie susceptibility. Ectopic expression of PrP in PrP knockout mice proved a useful tool for the identification of host cells competent for prion replication. Finally, the availability of PrP knockout mice and transgenic mice overexpressing PrP allows selective reconstitution experiments aimed at expressing PrP in neurografts or in specific populations of haemato- and lymphopoietic cells. The latter studies have allowed us to clarify some of the mechanisms of prion spread and disease pathogenesis.

Type
Research Article
Copyright
© The Physiological Society 2000

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