title: Genetic resistance to scrapie infection in experimentally challenged goats.
abstract: In goats, several field studies have identified coding mutations of the gene encoding the prion protein (I/M142, N/D146, S/D146, R/Q211, and Q/K222) that are associated with a lower risk of developing classical scrapie. However, the data related to the levels of resistance to transmissible spongiform encephalopathies (TSEs) of these different PRNP gene mutations are still considered insufficient for developing large-scale genetic selection against scrapie in this species. In this study, we inoculated wild-type (WT) PRNP (I142R154R211Q222) goats and homozygous and/or heterozygous I/M142, R/H154, R/Q211, and Q/K222 goats with a goat natural scrapie isolate by either the oral or the intracerebral (i.c.) route. Our results indicate that the I/M142 PRNP polymorphism does not provide substantial resistance to scrapie infection following intracerebral or oral inoculation. They also demonstrate that H154, Q211, and K222 PRNP allele carriers are all resistant to scrapie infection following oral exposure. However, in comparison to WT animals, the H154 and Q211 allele carriers displayed only moderate increases in the incubation period following i.c. challenge. After i.c. challenge, heterozygous K222 and a small proportion of homozygous K222 goats also developed the disease, but with incubation periods that were 4 to 5 times longer than those in WT animals. These results support the contention that the K222 goat prion protein variant provides a strong but not absolutely protective effect against classical scrapie.
authors.affiliation: INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacroux
authors.forename: Cécile
authors.initials: C
authors.lastname: Perrin-Chauvineau
authors.forename: Fabien
authors.initials: F
authors.lastname: Corbière
authors.forename: Naima
authors.initials: N
authors.lastname: Aron
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Calvo
authors.forename: Juan Maria
authors.initials: JM
authors.lastname: Torres
authors.forename: Pierrette
authors.initials: P
authors.lastname: Costes
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brémaud
authors.forename: Séverine
authors.initials: S
authors.lastname: Lugan
authors.forename: François
authors.initials: F
authors.lastname: Schelcher
authors.forename: Francis
authors.initials: F
authors.lastname: Barillet
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
mesh_terms: D000483:Alleles; D000818:Animals; D003062:Codon; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015511:Goat Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006041:Goats / Q000235:genetics; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism; D012608:Scrapie / Q000235:genetics*; D014018:Tissue Distribution
chemical_list: D003062:Codon; D018620:PrPSc Proteins