Sheep scrapie resistance

To address more fully the influence of the elk 132 polymorphism, transmissibility of CWD prions was assessed in transgenic mice expressing cervid PrPc with L or M at residue 132 [71]. While transgenic mice expressing CerPrP-L132 afforded partial resistance to CWD, SSBP/1 sheep scrapie prions transmitted efficiently to... 

Le Dur A, Beringue V, Andreoletti O, Reine F, Lai TL, Baron T, Bratberg B, Vilotte JL, Sarradin P, Benestad SL, Laude H (2005) A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes. Proc Natl Acad Sci USA 102 16031-16036... 

Jackson, G. S., Hosszu, L. L. R, Power, A., Hill, A. F., Kenney, J., Seiibil, H., Craven, C. J., Waltho, J. R, Qarke, A. R., and Collinge, J. 1999. Reversible conversion of monomeric human prion protein between native emd fibrilogenic conformations. Science 283 1935-1937 Jeffrey, M., Gonzalez, L., Espenes, A., Press, C. M., Martin, S., Chaplin, M., DAvis, L., Landsverk, T., MacAldowie, C., Eaton, S., and McGovern, G. 2006. Transportation of prion protein across the intestineil mucosa of scrapie-susceptible and scrapie-resistant sheep. J. Pathol. 209 4-14... 

Fig. 2 Cartoon of PrP allelic association with occurrence of classical scrapie and atypical/Nor98 scrapie. While classical scrapie occurs most frequently in sheep with VRQ and ARQ alleles, atypical/Nor98 scrapie occurs most frequently in AFRQ and AHQ PrP alleles. The presence of the ARR allele confers strong resistance towards classical scrapie, while this is not the case for atypical/Nor98 scrapie...

Atypical and classical forms of scrapie differ in a number of important respects. Sheep with atypical scrapie are invariably older, and cases are frequently only found in single animals in an infected flock [40]. Unlike the pathology of classical scrapie, there is little or no neuronal vacuolation or immunohistochemically-detect-able PrPSc in the obex region of the brain with atypical scrapie cases [37]. Abnormal PrP in atypical cases has been shown to be more susceptible to enzymatic digestion than in classical scrapie [41]. Also, characterization of protease-resistant PrPSc by Western blot shows a unique biochemical signature that is shared by all atypical scrapie cases, most prominently, a characteristic band of apparent low molecular weight 12 kDa that is not seen in analyses of classical scrapie cases [37]. Finally, atypical scrapie occurs in sheep with PRNP genotypes usually associated with resistance to classical scrapie, particularly with the AHQ allele. Sheep with atypical scrapie are more likely to express phenylalanine (F) than leucine (L) at codon 141 [40]. 

Specific mutations that appear in sheep in association with scrapie and the knowledge derived from sheep breeding allowing the selection of scrapie, and BSE-resistant animals, could not be confirmed in cattle as yet. 

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