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Title:   Author  item
                                            Greenlee, Justinitem
                                            Smith, Jodiitem
                                            Hamir, Amirali
  Submitted to: Research in Veterinary Science
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 2/21/2016
                                    Publication  Date: 4/1/2016
                                    Citation: Greenlee, J.J., Smith, J.D., Hamir, A.N. 2016. Oral inoculation of neonatal Suffolk sheep with the agent of classical scrapie results in PrPSc accumulation in sheep with the PRNP ARQ/ARQ but not the ARQ/ARR genotype. Research in Veterinary Science. 105:188–191.Interpretive Summary: Scrapie is a fatal disease of sheep and goats that causes damaging changes in the brain. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state and is resistant to breakdown by the host cells. The abnormal prion can cause the host's normal prion proteins to misfold and accumulate leading to neurologic disease. A sheep's susceptibility to scrapie is determined by their genetics. DNA encodes the host prion protein amino acid sequence, which is associated with resistance or susceptibility to the disease as different amino acids confer different folding properties to the intact protein. The amino acid in position 171 of the prion protein plays the biggest role in determining disease susceptibility. Sheep with the amino acid arginine (R) at 171 are resistant to scrapie while those with glutamine (Q) at that position are not. This study tested whether sheep with a single R allele at codon 171 (QR171) had a different response to the disease than those that were QQ171. The study determined that QR171were resistant to disease after oral exposure within the first 24 hours of life with a dose that caused disease in 100% of QQ171 sheep. This suggests that even one R allele at codon 171 (QR171) should protect lambs from exposure to highly infectious scrapie material. This result is important because our national scrapie eradication program is based on increasing the incidence of R171 in the national sheep flock. This information is useful to sheep farmers and breeders that are selectively breeding animals with genotypes resistant to scrapie and to regulators with roles in designing programs to enhance genetic resistance to scrapie.
                                Technical Abstract: Background
Scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent. 
Findings
This study reports the failure to detect PrPSc in nervous or lymphoid tissues of PRNP ARQ/ARR after oral inoculation with a U.S. scrapie isolate. Lambs were inoculated within the first 24 hours of birth with 1 ml of a 10% (wt./vol) brain homogenate derived from a clinically affected ARQ/ARQ sheep. The inoculated sheep were observed daily throughout the experiment for clinical signs suggestive of scrapie until they were necropsied at 86 months post inoculation. Tissues were collected for examination by immunohistochemistry and enzyme immunoassay, but all failed to demonstrate evidence of scrapie infection. 
Conclusions
Results of this study suggest that the dose of inoculum used in this study may have been below the threshold required to orally infect ARQ/ARR sheep at this age or ARQ/ARR sheep are resistant to infection with the U.S. scrapie isolate used.


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