title: Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie.
abstract: How susceptible pigs are to infection with sheep prions is unknown. We show, through transmission experiments in transgenic mice expressing porcine prion protein (PrP), that the susceptibility of this mouse model to bovine spongiform encephalopathy (BSE) can be enhanced after its passage in ARQ sheep, indicating that the pathogenicity of the BSE agent is modified after passage in sheep. Transgenic mice expressing porcine PrP were, nevertheless, completely resistant to infection with a broad panel of classical scrapie isolates from different sheep PrP genotypes and with different biochemical characteristics. The atypical (Nor98 like) isolate (SC-PS152) was the only scrapie isolate capable of transmission in these mice, although with a marked transmission barrier. Unexpectedly, the atypical scrapie agent appeared to undergo a strain phenotype shift upon transmission to porcine-PrP transgenic mice and acquired new strain properties, suggesting that atypical scrapie agent may exhibit different phenotypes depending on the host cellular PrP or other genetic factors.
authors.affiliation: Centro de Investigacion en Sanidad Animal, Madrid, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espinosa
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Herva
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
authors.forename: Danielle
authors.initials: D
authors.lastname: Padilla
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacroux
authors.forename: Hervé
authors.initials: H
authors.lastname: Cassard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lantier
authors.forename: Joaquin
authors.initials: J
authors.lastname: Castilla
authors.forename: Juan Maria
authors.initials: JM
authors.lastname: Torres
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002417:Cattle; D021821:Communicable Diseases, Emerging / Q000209:etiology / Q000473:pathology / Q000635:transmission / Q000662:veterinary; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000209:etiology* / Q000473:pathology / Q000635:transmission; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D012608:Scrapie / Q000209:etiology* / Q000473:pathology / Q000635:transmission; D012756:Sheep; D012757:Sheep Diseases / Q000209:etiology / Q000473:pathology / Q000635:transmission; D013045:Species Specificity; D013552:Swine
chemical_list: D011328:Prions; D011994:Recombinant Proteins