Use of a new immunoassay to measure PrP Sc levels in scrapie-infected sheep brains reveals PrP genotype-specific differences.
The diagnosis of prion diseases, such as scrapie and BSE, has traditionally relied upon the identification of the disease-associated form of the prion protein, PrP(Sc), based on its resistance to digestion by proteinase K (PK). A more recent development is the conformation-dependent immunoassay (CDI), which distinguishes between PrP Sc and normal PrP (PrP C) based on their differing solubility in guanidine hydrochloride rather than resistance or sensitivity to PK. We have developed a CDI-formatted sandwich immunoassay for the measurement of PrP Sc in sheep brain, which discriminates between clinically affected scrapie cases (natural or experimental) and uninfected controls of the same PrP genotype. Using this method, we have shown for the first time that, in sheep, the PrP genotype has a significant influence on the amount of PrP Sc deposited in the brains of animals experimentally infected with scrapie.
McCutcheon
S
S
Institute for Animal Health, Compton, Newbury, Berkshire, RG20 7NN, UK. sandra.mccutcheon@bbsrc.ac.uk
Hunter
N
N
Houston
F
F
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D005838:Genotype; D007118:Immunoassay / Q000379:methods*; D018621:PrPC Proteins / Q000235:genetics*; D018620:PrPSc Proteins / Q000032:analysis*; D012608:Scrapie / Q000175:diagnosis* / Q000235:genetics*; D012756:Sheep
D018621:PrPC Proteins; D018620:PrPSc Proteins