title: Goat K222-PrPCpolymorphic variant does not provide resistance to atypical scrapie in transgenic mice.
abstract: Host prion (PrPC) genotype is a major determinant for the susceptibility to prion diseases. The Q/K222-PrPCpolymorphic variant provides goats and mice with high resistance against classical scrapie and bovine spongiform encephalopathy (BSE); yet its effect against atypical scrapie is unknown. Here, transgenic mice expressing the goat wild-type (wt) or the K222-PrPCvariant were intracerebrally inoculated with several natural cases of atypical scrapie from sheep and goat and their susceptibility to the prion disease was determined. Goat wt and K222-PrPCtransgenic mice were 100% susceptible to all the atypical scrapie isolates, showing similar survival times and almost identical disease phenotypes. The capacity of the K222-PrPCvariant to replicate specifically the atypical scrapie strain as efficiently as the goat wt PrPC, but not the classical scrapie or cattle-BSE as previously reported, further suggests the involvement of concrete areas of the host PrPCin the strain-dependent replication of prions.
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.|Department of Pathology and Medicine, University of California San Diego (UCSD), La Jolla, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Calvo
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Espinosa
authors.affiliation: Interactions Hôte Agent Pathogène, École Nationale Vétérinaire de Toulouse, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
authors.affiliation: Animal and Plant Health Agency, Penicuik, Midlothian, UK.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: González
authors.affiliation: Instituto Nacional de Investigação Agrária e Veterinária, Lisbon, Portugal.
authors.forename: Leonor
authors.initials: L
authors.lastname: Orge
authors.affiliation: Neiker-Tecnalia, Derio, Vizcaya, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Juste
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain. jmtorres@inia.es.
authors.forename: Juan-María
authors.initials: JM
authors.lastname: Torres