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Blättler, T; Brandner, S; Raeber, A J; Klein, M A; Voigtländer, T; Weissmann, C; Aguzzi, A (1997). PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain. Nature, 389(6646):69-73.

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Abstract

Much available evidence points to a pathological isoform of the prion protein PrP being the infectious agent that causes transmissible spongiform encephalopathies, but the mechanisms controlling the neurotropism of prions are still unclear. We have previously shown that mice that do not express PrP (Prnp[o/o] mice) are resistant to infection by prions, and that if a Prnp(+/+) neurograft is introduced into such animals and these are infected intracerebrally with scrapie, the graft but not the surrounding tissue shows scrapie pathology. Here we show that PrP-expressing neurografts in Prnp(o/o) mice do not develop scrapie histopathology after intraperitoneal or intravenous inoculation with scrapie prions. Prion titres were undetectable in spleens of inoculated Prnp(o/o) mice, but were restored to wild-type levels upon reconstitution of the host lymphohaemopoietic system with PrP-expressing cells. Surprisingly, however, i.p. or i.v. inoculation failed to produce scrapie pathology in the neurografts of 27 out of 28 reconstituted animals, in contrast to intracerebral inoculation. We conclude that transfer of infectivity from the spleen to the central nervous system is crucially dependent on the expression of PrP in a tissue compartment that cannot be reconstituted by bone marrow transfer. Thus the requirement for the normal isoform of PrP in peripheral tissues represents a bottleneck for the spread of prions from peripheral sites to the central nervous system.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:04 September 1997
Deposited On:11 Feb 2008 13:25
Last Modified:23 Nov 2012 13:51
Publisher:Nature Publishing Group
ISSN:0028-0836
Publisher DOI:10.1038/37981
PubMed ID:9288968
Citations:Google Scholar™

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