NR AOYL
AU Ryder,S.J.; Heasman,L.; Warner,R.; Dexter,G.
TI Oral challenge of lambs with scrapie results in dramatically shortened incubation period: a new model for study of scrapie in sheep
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-01
PT Konferenz-Poster
AB
Natural scrapie has a long incubation period making study of the disease in the natural host difficult and expensive. Furthermore both incubation period and pathogenesis show considerable variation, in part related to PrP genotype. We report here a new model for the study of scrapie in the natural host with dramatically shortened and consistent incubation periods.
Inoculum comprised a pool of the entire brains of 17 scrapie affected sheep, homozygous or heterozygous for the VRQ and ARQ alleles of the PrP gene. Titration of this pool in mice (C57Bl) is in progress.
14 day old scrapie free Cheviot lambs of the VRQ/VRQ, VRQ/ARQ and VRQ/ARR genotypes were dosed orally with 1g or 5g of brain homogenate. Lambs were maintained on the ewe until normal weaning then housed indoors under normal agricultural conditions.
Infection occurred in all genotypes with highly consistent times to terminal disease ranging from approximately 7 months in VRQ/VRQ to 12 months in VRQ/ARR sheep. Control sheep challenged with normal brain and housed separately remain alive and well.
The transmissibility of experimental infection in 2 week lambs was shown by mixing 4 un-dosed V/V lambs with the challenged animals after a 28 day cleaning out period to avoid ingestion of excreted inoculum. Three of the four sheep have developed disease with incubation periods of approximately 21 months; 1 remains alive.
Influence of age at challenge was investigated by challenging 8 V/V lambs at 8 months of age. Times to terminal disease in these sheep were more variable, from 7 to 11 months and 2 animals remain alive 16 months post challenge.
Thus challenge of lambs orally at 2 weeks old provides a relatively rapid and reproducible model for the study of the pathogenesis of scrapie in the natural host; it resembles the natural disease in the sequential accumulation of prion protein in lymphoid and nervous tissues and is transmissible between sheep.
AD S.J. Ryder, G. Dexter, Veterinary Laboratories Agency, UK; L. Heasman, ADAS Consulting, UK; R. Warner, DEFRA, UK
SP englisch
PO Deutschland