Elk with a long incubation prion disease phenotype have a unique PrPd profile

• Published in: Neuroreport Vol. 18; no. 18; p. 1935
• Main Authors: O'Rourke, Katherine I, Spraker, Terry R, Zhuang, Dongyue, Greenlee, Justin J, Gidlewski, Thomas E, Hamir, Amir N
• Format: Journal Article
• Language: English
• Published: England 03.12.2007
• Subjects: Amino Acid Substitution - genetics; Animals; Brain - metabolism; Brain - physiopathology; Deer - genetics; Deer - metabolism; Gene Frequency - genetics; Genetic Predisposition to Disease - genetics; Genotype; Phenotype; Polymorphism, Genetic - genetics; Protein Folding; PrPC Proteins - chemistry; PrPC Proteins - genetics; PrPC Proteins - metabolism; Wasting Disease, Chronic - genetics; Wasting Disease, Chronic - metabolism; Wasting Disease, Chronic - physiopathology
• ISSN: 0959-4965
• DOI: 10.1097/WNR.0b013e3282f1ca2f

The transmissible spongiform encephalopathies (TSEs) invariably result in fatal neurodegeneration and accumulation of PrP, an abnormal form of the host prion protein PrP, encoded by the PRNP gene. A naturally occurring polymorphism (methionine/valine) at PRNP codon 129 is associated with variation in relative disease susceptibility, incubation time, clinical presentation, neuropathology, and/or PrP biochemical characteristics in a range of human TSEs. A methionine/leucine polymorphism at the corresponding site in the Rocky Mountain elk PRNP gene is associated with variation in relative susceptibility and incubation time in the cervid TSE chronic wasting disease. We now report that elk lacking the predisposing 132-methionine allele develop chronic wasting disease after a long incubation period and display a novel PrP folding pattern.