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Title:   Author  item
                                            Greenlee, Justinitem
                                            Nicholson, Ericitem
                                            Kunkle, Robertitem
                                            Hamir, Amirali
  Submitted to: Meeting Abstract
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 6/20/2009
                                    Publication  Date: 9/23/2009
                                    Citation: Greenlee, J.J., Nicholson, E.M., Kunkle, R.A., Hamir, A.N. 2009. Prolonged Incubation Time in Sheep with QK171 Genotype [abstract]. Prion 2009. p. 120.Interpretive Summary:
                                Technical Abstract: Background: Sheep scrapie susceptibility or resistance is a function of genotype with polymorphisms at codon 171 playing a major role.  Glutamine (Q) at 171 contributes to scrapie susceptibility while arginine (R) is associated with resistance.  In some breeds, lysine (K) occurs at 171, but its affect on scrapie resistance has not been studied.
   Objectives: Charge and structural similarities between K and R would suggest that they may contribute to prion disease susceptibility in a similar way, but studies have not been done to confirm this. The purpose of this study was to determine and compare susceptibility of sheep with QQ171 and QK171 genotypes.
   Methods: We inoculated Barbado sheep ARQ/ARQ and ARK/ARQ with scrapie (NADC 13-7) by intracerebral inoculation to assess the susceptibility of these sheep to scrapie. After inoculation, sheep were observed daily for clinical signs and were euthanized and necropsied after clinical signs were unequivocal. Tissues were collected at necropsy for immunohistochemistry and western blot.
   Results: QQ171 sheep had clinical signs an average of 12 months after inoculation whereas QK animals had an incubation time of 30 months to average onset of clinical signs. The distribution of PrP**Sc was similar in QQ171 and QK171 sheep.
   Discussion: Sheep with a single K allele at 171 are susceptible to scrapie, but with a prolonged incubation time. Studies are underway to determine the relative susceptibility or resistance of sheep with KK171.


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