Submitted to: United States Animal Health Association Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 10/20/2007
Publication Date: 10/20/2007
Publication URL: http://www.usaha.org/meetings/proceedings.shtml
Citation: Greenlee, J.J., O'Rourke, K.I., Hamir, A.N., Gidlewski, T., Zhuang, D., Spraker, T. 2007. Prolonged CWD Incubation Time and Unique PrP**d Profile in Prnp 132LL Elk. In: Proceedings of the U.S. Animal Health Association 111th Annual Meeting, Captive Wildlife and Alternative Livestock Committee, October 20, 2007, Reno, Nevada. p. 264-265. Interpretive Summary:
Technical Abstract: The transmissible spongiform encephalopathies including chronic wasting disease (CWD) in deer and elk invariably result in fatal neurodegeneration and accumulation of PrP**d, an abnormal form of the host prion protein PrP**c. In some species, polymorphisms in the open reading frame of the Prnp gene are associated with differences in the manifestation of prion disease including relative susceptibility, clinical signs, incubation time, and neuropathology. The polymorphism (M to L) at Prnp 132 in Rocky Mountain Elk (Cervus elaphus nelsoni) corresponds to the human (M to V) polymorphism at Prnp 129, which has been associated with susceptibility to vCJD. Elk with 132 M alleles are predisposed to CWD and heterozygosity is associated with a prolonged incubation time following experimental challenge. Previous studies suggest that elk homozygous for 132 L occur rarely and make up the extreme minority of elk affected with CWD. The effect of the 132 LL genotype on the development of CWD post-exposure was previously unknown. The purpose of this study was to define the course of disease in elk with various Prnp 132 allele combinations. Elk (n=8; 2MM, 2LM, 4LL) were orally inoculated at 8 months of age with 15 ml of pooled brain homogenate from one 132 MM and one 132 LM elk. Elk were observed daily after inoculation and necropsies were done when clinical signs became unequivocal. Immunohistochemistry (IHC), western blot, and microscopic examination were used to confirm infection. Incubation time was dependent on genotype. Clinical signs were apparent in 132 MM elk after 23 months and 132 LM elk after 40 months. Rectal biopsies were done on the remaining 132 LL elk with 3 of 4 testing positive for PrP**d by IHC indicating peripheral distribution of PrP**d is apparent prior to the onset of clinical disease. Clinical signs were apparent in 132 LL elk after 59-63 months. One elk was euthanized 63 months post-inoculation without exhibiting clinical signs, but had PrP**d accumulation in CNS and peripheral lymphoid tissues. Differences between genotype were apparent after western blot analysis. The molecular weight of the proteinase K resistant bands of PrP**d is lower in the 132LL elk compared to 132MM or 132LM elk. In summary, LL elk are susceptible to CWD, but have a prolonged incubation time and western blot profile unique from other genotypes of elk with CWD. Additional studies are planned to determine the mechanisms responsible for the distinct presentation of CWD in 132 LL elk.