Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie.
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.
Espinosa
Juan Carlos
JC
Centro de Investigacion en Sanidad Animal, Madrid, Spain.
Herva
María Eugenia
ME
Andréoletti
Olivier
O
Padilla
Danielle
D
Lacroux
Caroline
C
Cassard
Hervé
H
Lantier
Isabelle
I
Castilla
Joaquin
J
Torres
Juan Maria
JM
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
D011328:Prions; D011994:Recombinant Proteins