title: Effects of polymorphisms in ovine and caprine prion protein alleles on cell-free conversion.
abstract: In sheep polymorphisms of the prion gene (PRNP) at the codons 136, 154 and 171 strongly influence the susceptibility to scrapie and bovine spongiform encephalopathy (BSE) infections. In goats a number of other gene polymorphisms were found which are suspected to trigger similar effects. However, no strong correlation between polymorphisms and TSE susceptibility in goats has yet been obtained from epidemiological studies and only a low number of experimental challenge data are available at present. We have therefore studied the potential impact of these polymorphisms in vitro by cell-free conversion assays using mouse scrapie strain Me7. Mouse scrapie brain derived PrPSc served as seeds and eleven recombinant single mutation variants of sheep and goat PrPC as conversion targets. With this approach it was possible to assign reduced conversion efficiencies to specific polymorphisms, which are associated to low frequency in scrapie-affected goats or found only in healthy animals. Moreover, we could demonstrate a dominant-negative inhibition of prion polymorphisms associated with high susceptibility by alleles linked to low susceptibility in vitro.
authors.affiliation: Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, D-17493 Greifswald-Insel Riems, Germany. martin.groschup@fli.bund.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Eiden
authors.forename: Elizabeth Ortega
authors.initials: EO
authors.lastname: Soto
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
authors.forename: Martin H
authors.initials: MH
authors.lastname: Groschup
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004198:Disease Susceptibility / Q000662:veterinary; D015511:Goat Diseases / Q000235:genetics*; D006041:Goats; D051379:Mice; D009154:Mutation; D011110:Polymorphism, Genetic; D011328:Prions / Q000235:genetics* / Q000378:metabolism*; D012608:Scrapie / Q000235:genetics*; D012756:Sheep
chemical_list: D011328:Prions