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Determine the extent and biological effect of strain variation in chronic wasting disease using transgenic mouse models.
APPROACH: Candidate preparations of brain from sheep, goats, deer, and elk naturally infected with transmissible spongiform encephalopathy (TSE) agents of North American origin will be characterized by genetic and biochemical methods, including DNA sequence analysis of the PRNP open reading frame, glycoform analysis on western blot, and PrP-d distribution in the brain and lymphoid tissues and by epidemiology, including geographic location of the animal and potential exposure to TSEs from other species. Prioritization of candidates will be based on western blot patterns, potential exposure to TSEs of other species, and genotype, with other factors considered if sufficient numbers of Tg mice are available. Samples will be assayed in Tg mice expressing the cervid and/or ovine PRNP gene. Disease in the recipient mice will be characterized by incubation time, PrP-d distribution, intensity, and glycoform patterns, and microscopic lesion patterns. Results will be compared to those produced by well characterized isolates of ovine scrapie. BSL-1; 9-4-06. Documents SCA with U. of KY. Formerly 5348-32000-021-06S December 2006.
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PROGRESS: 2005/10 TO 2006/09
Progress Report 4d Progress report. This report serves to document research conducted under a specific cooperative agreement between ARS and the University of Kentucky. Additional details of research can be found in the report for the parent project 5348-32000-021-00D BSE and other TSEs Ruminant Herbivors: Diagnosis, Transmission and Genetics. Transgenic mice expressing the cervid prion were inoculated with homogenates of brain and a peripheral highly vascularized tissue (antler velvet). This work is conducted in collaboration with the Canadian Food Inspection Agency, in an effort to harmonize results from North American cervids. The mice are being observed for clinical disease and extensive histopathology and biochemical analysis of brain tissue in the recipient mice will be conducted when the mice reach clinical disease or senescence.