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About the Authors:
Justin J. Greenlee
* E-mail: [email protected]
Affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, United States of America
Robert A. Kunkle
Affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, United States of America
Jürgen A. Richt
Current address: Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, United States of America
Affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, United States of America
Eric M. Nicholson
Affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, United States of America
Amir N. Hamir
† Deceased.
Affiliation: Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, United States of America
Introduction
Scrapie is a horizontally transmitted, uniformly fatal neurodegenerative disease of sheep and goats. Definitive diagnosis is typically defined by postmortem pathology and detection of the disease-specific prion protein, called PrPSc, in affected tissues. [1] Most scrapie infections are presumably acquired by the oral route. Exposure to the scrapie agent initiates an autocatalytic, templated conversion of the highly conserved, host-encoded, membrane-anchored glycoprotein PrPC to the abnormally folded PrPSc. The clinical and pathological hallmarks of scrapie develop as PrPSc gradually accumulates in the central nervous system (CNS) months or years after initial exposure.
At the clinical stage of scrapie, PrPSc is widely distributed throughout the CNS and is associated with microscopic evidence of neuronal vacuoles, neuronal loss, astrocytosis, and generalized vacuolation of the neuropil. Lymphoid tissues also can accumulate PrPSc in scrapie-affected sheep, and immunohistochemical (IHC) detection of PrPSc in palatine tonsil, [2] third eyelid, [3] or gut-associated lymphatic tissue of the rectal mucosa [4] of sheep has been used for the diagnosis of scrapie at either the preclinical or clinical stage of disease.
The susceptibility of sheep to scrapie is greatly influenced by host prion protein gene (PRNP) alleles. Amino-acid polymorphisms corresponding to the codons 136, 154 and 171 are major determinants of relative...