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Astrocyte‐specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie
Author(s) -
Raeber Alex J.,
Race Richard E.,
Brandner Sebastian,
Priola Suzette A.,
Sailer Andreas,
Bessen Richard A.,
Mucke Lennart,
Manson Jean,
Aguzzi Adriano,
Oldstone Michael B.A.,
Weissmann Charles,
Chesebro Bruce
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.20.6057
Subject(s) - biology , scrapie , hamster , library science , prion protein , pathology , medicine , microbiology and biotechnology , disease , computer science
Transmissible spongiform encephalopathies are characterized by spongiosis, astrocytosis and accumulation of PrP Sc , an isoform of the normal host protein PrP C . 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 PrP Sc 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.