NR AXIC
AU Angers,R.C.; Browning,S.R.; Seward,T.S.; Miller,M.W.; Balachandran,A.; McKenzie,D.; Hoover,E.A.; Telling,G.C.
TI Characterization of CWD Prion Strains Uding Transgenic Mice
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.42
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Although the distribution and host range of chronic wasting disease (CWD) is increasing, whether or not different CWD strains occur in various geographic locations or in different cervid species remains unclear. To address this we used cervidized transgenic mice (Tg(CerPrP)1536) to analyze CWD prions isolated from mule deer, white-tailed deer and elk from various geographic locations in North America. Isolates were characterized on the basis of incubation times in Tg(CerPrP)1536 mice. In all cases serial transmissions were performed in Tg(CerPrP)1536 mice. The biochemical properties of CerPrPsc produced in the brains of diseased mice were assessed by western blotting and conformational stability assays. We also used histoblot analysis to obtain a global portrait of the neuroanatomical distribution of CerPrPsc in the brains of diseased Tg(CerPrP)1536 mice in conjunction with immunohistochemical staining and hematoxylin and eosin staining to more fully characterize neuropathology. The glycosylation ratios of CerPrPsc were similar for all samples analyzed with the diglycosylated species of CerPrPsc being chiefly represented. Additionally, the stability of CerPrPsc, assessed by treatment with increasing concentrations of guanidine hydrochloride, demonstrated that the various CWD isolates were associated with similar conformations of CerPrPsc. Consistent with these results, there was little variation in the mean incubation times of CWD samples originating from different locations or species. However, while most inoculated Tg(CerPrP)1536 mice developed prion disease around 200 days post-inoculation, occasionally the incubation time of CWD prions approached 300 days. The neuropathological profile of mice Tg(CerPrP)1536 mice with more rapid incubation times consisted of extensive CerPrPsc deposition in the corpus callosum and frequently the hippocampus with corresponding neuronal vacuolation. In contrast, Tg(CerPrP)1536 mice with longer incubation times profiles displayed an unsystematic pattern of CerPrPsc deposition and vacuolation with irregular large plaques scattered throughout the brain and no CerPrPsc accumulation in the corpus callosum. Our data suggest the existence of one prevailing CWD strain in the United States and Canada, and raise the possibility of a co-existing second strain in some cases.
AD R.C. Angers, S.R. Browning, University of Kentucky, Microbiology, Immunology and Molecular Genetics, USA; T.S. Seward, G.C. Telling, University of Kentucky, Sanders Brown Center on Aging, USA; M.W. Miller, Wildlife Research Center, Colorado Division of Wildlife, USA; A. Balachandran, Canadian Food Inspection Agency, Animal Diseases Research Institute, Canada; D. McKenzie, University of Wisconsin, School of Veterinary Medicine, USA; E.A. Hoover, Colorado State University, Microbiology, Immunology and Pathology, USA
SP englisch
PO Schottland