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Title:   Author  item
                                            Greenlee, Justinitem
                                            ZHANG, XIA - Iowa State Universityitem
                                            Nicholson, Ericitem
                                            Kunkle, Robertitem
                                            Hamir, Amirali
  Submitted to: Journal of Veterinary Diagnostic Investigation
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 12/20/2011
                                    Publication  Date: 5/1/2012
                                    Citation: Greenlee, J.J., Zhang, Xia, Nicholson, E.M., Kunkle, R.A., Hamir, A.N. 2012. Prolonged incubation time in sheep with prion protein containing lysine at position 171. Journal of Veterinary Diagnostic Investigation. 24(3):554-558.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. Whether or not a sheep will get scrapie is determined by their genetics. A change in the DNA that codes for the host prion protein will cause the animal to be either resistant or susceptible to the disease. A specific location on this gene, codon 171, seems to play 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. It has been suggested that lysine (K) at 171 may behave similarly to R because the two amino acids have a similar structure. This study tested whether sheep with a single k allele at codon 171 (QK171) had a different response to the disease than those that were QQ171. The study determined that while QK171 were not resistant to the disease, they took longer to develop scrapie than QQ171 sheep. Further studies are underway to determine if two k alleles (KK171) protects from developing scrapie or if animals with the KK171 genotype have further prolongation of incubation time. This information is useful to sheep farmers and breeders that are selectively breeding animals with genotypes resistant to scrapie.
                                Technical Abstract: Sheep scrapie susceptibility or resistance is a function of genotype with polymorphisms at codon 171 in the sheep prion gene 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 codon 171, but its affect on scrapie resistance has not been determined. 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 performed to confirm this. The purpose of this study was to compare susceptibility and incubation times of AA136RR154QQ171 (where the letter denotes the amino acid and the number the position) with AA136RR154QK171  sheep after inoculation with scrapie. Barbado AA136RR154QQ171 and AA136RR154QK171 sheep were inoculated with scrapie intracerebrally to assess their susceptibility 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 analyses. QQ171 sheep had clinical signs approximately 12 months after inoculation, whereas QK171 animals had an average incubation time of 30 months to onset of clinical signs. The distribution of PrP**Sc was similar in QQ171 and QK171 sheep. Results of this study indicate that sheep with a single K allele at 171 are susceptible to scrapie, but with a prolonged incubation time. Work is currently underway to examine relative scrapie susceptibility or resistance of KK171 sheep.


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