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Raeber, A J; Race, R E; Brandner, S; Priola, S A; Sailer, A; Bessen, R A; Mucke, L; Manson, J C; Aguzzi, A; Oldstone, M B; Weissmann, C; Chesebro, B (1997). Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO Journal, 16(20):6057-6065.

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Abstract

Transmissible spongiform encephalopathies are characterized by spongiosis, astrocytosis and accumulation of PrPSc, an isoform of the normal host protein PrPC. The exact cell types responsible for agent propagation and pathogenesis are still uncertain. To determine the possible role of astrocytes, we generated mice devoid of murine PrP but expressing hamster PrP transgenes driven by the astrocyte-specific GFAP promoter. After inoculation with hamster scrapie, these mice accumulated infectivity and PrPSc to high levels, developed severe disease after 227 +/- 5 days and died 7 +/- 4 days later. Therefore, astrocytes could play an important role in scrapie pathogenesis, possibly by an indirect toxic effect on neurons. Interestingly, mice expressing the same transgenes but also endogenous murine PrP genes propagated infectivity without developing disease.

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1997
Deposited On:11 Feb 2008 13:26
Last Modified:27 Nov 2013 18:28
Publisher:Nature Publishing Group
ISSN:0261-4189
Publisher DOI:10.1093/emboj/16.20.6057
PubMed ID:9321385
Citations:Web of Science®. Times Cited: 136
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