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Title: Detection of the Abnormal Isoform of the Prion Protein Associated With Chronic Wasting Disease in the Optic Pathways of the Brain and Retina of Rocky Mountain Elk (Cervus elaphus nelsoni)

item SPRAKER, TERRY - Colorad0 State University
item O'Rourke, Katherine
item GIDLEWSKI, T - Animal And Plant Health Inspection Service (APHIS)
item POWERS, J - National Park Service
item Greenlee, Justin
item WILD, M - National Park Service

Submitted to: Veterinary Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/28/2009
Publication Date: 4/9/2010
Citation: Spraker, T.R., Orourke, K.I., Gidlewski, T.L., Powers, J., Greenlee, J.J., Wild, M.A. 2010. Detection of the Abnormal Isoform of the Prion Protein Associated With Chronic Wasting Disease in the Optic Pathways of the Brain and Retina of Rocky Mountain Elk (Cervus elaphus nelsoni). Veterinary Pathology. 47(3):536-546.

Interpretive Summary: Chronic wasting disease is a prion disorder of Rocky Mountain elk, white tailed deer, mule deer, and moose in limited areas of North America. The disorder shares some similarities with scrapie of sheep and goats but it is notably different in the distribution and amount of abnormal prion protein in the brain and peripheral tissues. Systematic analysis of the spread of the abnormal prion protein through the tissues of the elk is limited by the difficulties of working with large wild ruminants in a research setting, as well as the possibility that the experimental route of infection results in a different disease pattern than is seen in natural disease. In this study, wild elk and elk with experimental disease were examined for the pattern of accumulation of abnormal prion proteins in the optic nerve and the eye. In a small sample of captive elk, the disease stage was estimated from the time of infection and the interval to progression to clinical disease. In wild elk, disease stage was estimated from the extent of prion protein accumulation in the brain. Abnormal prion protein was found in the eye only in elk with relatively advanced disease. The prion gene sequence determines the length of incubation time in elk with experimental disease. In this study, elk with the long incubation genotype had a notably different pattern of abnormal prion protein accumulation in the eye and a different pattern of prion protein processing by the cells of the retina. The study demonstrates that prion genotype is critical to our understanding of prion protein processing in the nervous system of the elk.

Technical Abstract: Eyes and nuclei of the visual pathways in the brain from 30 Rocky Mountain elk representing 3 PRNP genotypes, naturally or experimentally infected with chronic wasting disease, a prion disease of deer and elk. Elk were scored for relative disease progression by immunohistochemistry analysis of the abnormal prion protein as well as spongiform degeneraton at 9 neuroanatomic locations in the medulla at the level of the obex. Immunohistochemistry assay and epitope mapping of the abnormal prion protein was performed on sites along the visual from the superior colliculus to the retina. The study demonstrated that the abnormal prion was disseminated along the visual pathway beginning in the middle stages of disease, reaching the retina only in elk with an obex score of 4 on a 5 point scale. Processing of the protein in the neural cells of the pathway was similar to that observed in vitro, with a shift in the endogenous protease cleavage site in elk of the gentoype associate with long incubation. There was no difference between the elk with the short or medium incubation phenotypes associated with homozygosity or heterozygosity for the wild type prion gene allele. An understanding of the movement and processing of the abnormal prion from the brain to the periphery will be useful in understanding the clinical outcome of the disease in elk and the role of a single amino acid residue in controlling prion folding.