title: Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie.
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.
authors.affiliation: Institut für Molekularbiologie, Abteilung I, University of Zürich, H-onggerberg, 8093 Z-urich, Switzerland.
authors.forename: A J
authors.initials: AJ
authors.lastname: Raeber
authors.forename: R E
authors.initials: RE
authors.lastname: Race
authors.forename: S
authors.initials: S
authors.lastname: Brandner
authors.forename: S A
authors.initials: SA
authors.lastname: Priola
authors.forename: A
authors.initials: A
authors.lastname: Sailer
authors.forename: R A
authors.initials: RA
authors.lastname: Bessen
authors.forename: L
authors.initials: L
authors.lastname: Mucke
authors.forename: J
authors.initials: J
authors.lastname: Manson
authors.forename: A
authors.initials: A
authors.lastname: Aguzzi
authors.forename: M B
authors.initials: MB
authors.lastname: Oldstone
authors.forename: C
authors.initials: C
authors.lastname: Weissmann
authors.forename: B
authors.initials: B
authors.lastname: Chesebro
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001681:Biological Assay; D001921:Brain / Q000473:pathology; D006224:Cricetinae; D004198:Disease Susceptibility; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018620:PrPSc Proteins / Q000096:biosynthesis / Q000235:genetics; D011328:Prions / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012376:Rodent Diseases / Q000209:etiology* / Q000401:mortality; D012608:Scrapie / Q000209:etiology* / Q000401:mortality
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018620:PrPSc Proteins; D011328:Prions; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins