title: Ovine prion protein variant A(136)R(154)L(168)Q(171) increases resistance to experimental challenge with bovine spongiform encephalopathy agent.
abstract: Susceptibility and incubation periods of transmissible spongiform encephalopathies, such as scrapie in sheep, are modulated by the PrP gene. The standard model of association between ovine PrP genetics and classical scrapie susceptibility is based on PrP genotypes with respect to codons 136, 154 and 171, e.g. alanine-arginine-glutamine (ARQ). It is demonstrated here that a proline to leucine substitution in codon 168 of the ovine PrP protein gene is associated with increased resistance to experimental bovine spongiform encephalopathy (BSE) inoculation. The ARL(168)Q PrP allele was found in heterozygous ARP(168)Q/ARL(168)Q sheep that have so far survived intravenous BSE challenge three times longer than BSE-challenged homozygous ARP(168)Q/ARP(168)Q sheep, which develop disease in around 700 days. In contrast, the L141F polymorphism does not appear to be associated with susceptibility to intravenous BSE challenge.
authors.affiliation: Institute for Animal Health (IAH), Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Goldmann
authors.affiliation: IAH, Compton Laboratory, Compton, Berkshire RG20 7NN, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Houston
authors.affiliation: Institute for Animal Health (IAH), Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Stewart
authors.affiliation: Institute for Animal Health (IAH), Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK.
authors.forename: Matteo
authors.initials: M
authors.lastname: Perucchini
authors.affiliation: Institute for Animal Health (IAH), Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK.
authors.forename: James
authors.initials: J
authors.lastname: Foster
authors.affiliation: Institute for Animal Health (IAH), Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK.
authors.forename: Nora
authors.initials: N
authors.lastname: Hunter
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D005838:Genotype; D006579:Heterozygote; D007113:Immunity, Innate / Q000235:genetics*; D011110:Polymorphism, Genetic; D017096:Prion Diseases / Q000235:genetics*; D011328:Prions / Q000235:genetics*; D012756:Sheep; D013534:Survival
chemical_list: D011328:Prions