title: Disease phenotype in sheep after infection with cloned murine scrapie strains.
abstract: Prion diseases exhibit different disease phenotypes in their natural hosts and when transmitted to rodents, and this variability is regarded as indicative of prion strain diversity. Phenotypic characterization of scrapie strains in sheep can be attempted by histological, immunohistochemical and biochemical approaches, but it is widely considered that strain confirmation and characterization requires rodent bioassay. Examples of scrapie strains obtained from original sheep isolates by serial passage in mice include ME7, 79A, 22A and 87V. In order to address aspects of prion strain stability across the species barrier, we transmitted the above murine strains to sheep of different breeds and susceptible Prnp genotypes. The experiment included 40 sheep dosed by the oral route alone and 36 sheep challenged by combined subcutaneous and intracerebral routes. Overall, the combined route produced higher attack rates (~100%) than the oral route (~50%) and 2-4 times shorter incubation periods. Uniquely, 87V given orally was unable to infect any sheep. Overall, scrapie strains adapted and cloned in mice produce distinct but variable disease phenotypes in sheep depending on breed or Prnp genotype. Further re-isolation experiments in mice are in progress in order to determine whether the original cloned murine disease phenotype will reemerge.
authors.affiliation: Department of Pathology, Animal Health and Veterinary Laboratories Agency (AHVLA-Lasswade), Pentlands Science Park, Midlothian, UK. ssiso@ucdavis.edu
authors.forename: Silvia
authors.initials: S
authors.lastname: Sisó
authors.forename: Francesca
authors.initials: F
authors.lastname: Chianini
authors.forename: Sam L
authors.initials: SL
authors.lastname: Eaton
authors.forename: Janey
authors.initials: J
authors.lastname: Witz
authors.forename: Scott
authors.initials: S
authors.lastname: Hamilton
authors.forename: Stuart
authors.initials: S
authors.lastname: Martin
authors.forename: Jeanie
authors.initials: J
authors.lastname: Finlayson
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Pang
authors.forename: Paula
authors.initials: P
authors.lastname: Stewart
authors.forename: Philip
authors.initials: P
authors.lastname: Steele
authors.forename: Mark P
authors.initials: MP
authors.lastname: Dagleish
authors.forename: Wilfred
authors.initials: W
authors.lastname: Goldmann
authors.forename: Hugh W
authors.initials: HW
authors.lastname: Reid
authors.forename: Martin
authors.initials: M
authors.lastname: Jeffrey
authors.forename: Lorenzo
authors.initials: L
authors.lastname: González
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001923:Brain Chemistry; D018604:Epitope Mapping; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010641:Phenotype; D011328:Prions / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry; D012608:Scrapie / Q000145:classification* / Q000235:genetics / Q000473:pathology / Q000635:transmission; D012756:Sheep; D013045:Species Specificity; D014630:Vagus Nerve / Q000737:chemistry / Q000473:pathology
chemical_list: D006023:Glycoproteins; D011328:Prions; D020033:Protein Isoforms