NR AXOW
AU Hunter,N.; Foster,J.; Goldmann,W.; Houston,F.; Parnham,D.; Drummond,D.; Halliday,S.; Gossner,A.; Hopkins,J.
TI Pathogenesis Studies of SSBP/1 Scrapie in New Zealand Sheep of a Range PrP Genotypes Show Susceptibility Differences from UK Sheep
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.166
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
SSBP/1 is a source of experimental scrapie which has been used in NPU Cheviot sheep for many decades. It causes clinical disease in sheep with PrP genotypes encoding at least one VRQ allele. Following subcutaneous (sc) inoculation, VRQ/VRQ animals succumb to scrapie in around 160 days, whereas heterozygotes have longer incubation periods of ~260 days (VRQ/ARQ) and ~360 days (VRQ/ARR and VRQ/AHQ). All other NPU Cheviot genotypes including ARQ/ARQ are resistant to SSBP/1 (sc). However New Zealand (NZ) sheep were different: VRQ/VRQ animals had shortest incubation periods (~150 days) but VRQ heterozygotes (we tested VRQ/ARQ and VRQ/ARR) had the same incubation periods of ~260 days. Pathogenesis studies of SSBP/1 in the susceptible genotypes have revealed the timing of spread of infection (using PrPsc as a marker) from peripheral lymphoreticular tissue to the brain is much slower in VRQ/ARR animals (NZ sheep) than VRQ/VRQ, with implications for development of diagnostic tests.
Why do VRQ/ARR animals in the NPU Cheviot flock have 360 day incubation periods whereas NZ VRQ/ARR animals develop disease around 100 days earlier? In addition, ARQ/ARQ NZ sheep were not resistant to SSBP/1 challenge but became scrapie affected >1,000 days following challenge. This is likely not to be related to the SSBP/1 titre - SSBP/1 is being titred for the first time in transgenic mice and shows very high levels of infectivity. There may be additional genetic differences between the two groups of sheep (NPU and NZ) , other than the PrP gene three codon genotype. We have carried out single nucleotide polymorphism analyses of the PrP gene non-coding regions and it is clear that the VRQ, ARR and ARQ alleles are not single haplotypes so it is possible that this heterogeneity contributes to the biological effects observed.
AD N. Hunter, J. Foster, W. Goldmann, D. Parnham, D. Drummond, Roslin Institute, Neuropathogenesis Unit, UK; F. Houston, S. Halliday, Roslin Institute, Neuropathogenesis Unit, Compton, UK; A. Gossner, J. Hopkins, University of Edinburgh, Veterinary Biomedical Sciences, R(D)SVS, UK
SP englisch
PO Schottland