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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1858

Brandner, S; Raeber, A; Sailer, A; Blättler, T; Fischer, M B; Weissmann, C; Aguzzi, A (1996). Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 93(23):13148-13151.

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Mice devoid of PrPC (Prnp%) are resistant to scrapie and do not allow propagation of the infectious agent (prion). PrPC-expressing neuroectodermal tissue grafted into Prnp% brains but not the surrounding tissue consistently exhibits scrapie-specific pathology and allows prion replication after inoculation. Scrapie prions administered intraocularly into wild-type mice spread efficiently to the central nervous system within 16 weeks. To determine whether PrPC is required for scrapie spread, we inoculated prions intraocularly into Prnp% mice containing a PrP-overexpressing neurograft. Neither encephalopathy nor protease-resistant PrP (PrPSc) were detected in the grafts for up to 66 weeks. Because grafted PrP-expressing cells elicited an immune response that might have interfered with prion spread, we generated Prnp% mice immunotolerant to PrP and engrafted them with PrP-producing neuroectodermal tissue. Again, intraocular inoculation did not lead to disease in the PrP-producing graft. These results demonstrate that PrP is necessary for prion spread along neural pathways.


170 citations in Web of Science®
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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:12 November 1996
Deposited On:11 Feb 2008 12:26
Last Modified:05 Apr 2016 12:20
Publisher:National Academy of Sciences
Publisher DOI:10.1073/pnas.93.23.13148
Related URLs:http://www.pnas.org/cgi/content/full/93/23/13148
PubMed ID:8917559

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