Degree Type

Thesis

Date of Award

2018

Degree Name

Master of Science

Department

Theses & dissertations (Interdisciplinary)

Major

Neuroscience

First Advisor

M. Heather Greenlee

Abstract

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect both humans and animals. TSEs, or prion diseases, are associated with the accumulation of the misfolded prion protein (PrPSc) in central and peripheral nervous system, and lymphoid tissues. Accumulation of PrPSc results from the misfolding of the normal, cellular prion protein (PrPC) to the disease-associated form (PrPSc). TSEs have strain variations that can affect host susceptibility, incubation period, and disease phenotype, including PrPSc accumulation intensity and patterning. These strain variations also influence interspecies transmission. It has been demonstrated that white-tailed deer are susceptible to the scrapie agent (the TSE of sheep). However, sheep are not very susceptible to the CWD agent. The purpose of this thesis was to determine the susceptibility of sheep to the scrapie agent derived from white-tailed deer (WTD-scrapie).

Suffolk sheep of various genotypes were challenged oronasally with the WTD-scrapie agent from either deer cerebrum or brainstem at the level of the obex. We found that sheep with a valine (V) at codon 136 (VV136) of the prion protein (PRNP) had a shorter incubation period than sheep with an alanine (A) at codon 136 (AA136). This result is in contrast to the original sheep scrapie agent that had a faster incubation period in AA136 sheep. We observe differences in PrPSc accumulation intensity and spongiform change between sheep of different genotypes challenged with the same inoculum source and sheep of the same genotype challenged with different inocula. We also demonstrated that inocula prepared from sheep challenged with the WTD scrapie agent resulted in a reduced incubation period in transgenic mice expressing ovine PRNP when compared to the original sheep scrapie isolate. The results presented in this thesis demonstrate that sheep are susceptible to the scrapie agent derived from WTD and the phenotype of disease is different than the original sheep scrapie inoculum source.

Copyright Owner

Robyn Kokemuller

Language

en

File Format

application/pdf

File Size

79 pages

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