Scrapie resistance

Protocols has been developed for several applications and are available from the manufacturer. Multiplex sequencing (analysis of more than one sequence per reaction) is also possible with optimized protocols, depending on the sequences following the primers (e.g., screening for scrapie resistance). In this case the sequence detected has to be compared to reference samples because at multiplex analysis the sequence received is a combination from reactions with different primers. 

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... 

Kocisko DA, Priola SA, Raymond GJ, Chesebro B, Lansbury PT Jr, Caughey B. Species specificity in the cell-free conversion of prion protein to protease-resistant forms a model for the scrapie species barrier. Proc Natl Acad USA 1995 92 3923-3927. 

The normal cellular form of prion protein (PrPc) can exist as a Cu-metalloprotein in vivo (492). This PrPc is a precursor of the pathogenic protease-resistant form PrPsc, which is thought to cause scrapie, bovine spongiform encephalopathy (BSE), and Creutzfeldt—Jakob disease. Two octa-repeats of PHGGGWGQ have been proposed as Cu(II) binding sites centered on histidine (493). They lack secondary and tertiary structure in the absence of Cu(II). Neurons may therefore have special mechanisms to regulate the distribution of copper. 

A large fraction of polytungstates that have been tested prove to have potent antitumoral and antiviral activity (rabies, influenza, scrapie, and the retroviruses responsible for AIDS and SAIDS). Toxicity varies widely, bnt some species are less toxic than azidothymidine (AZT) and are effective against AZT-resistant cell lines. The polyoxoanions bind to the gpl20 envelope glycoprotein of the retrovirus, and in some cases inhibit the function of the rus reverse transcriptase (cf AZT). Reviews of Structure and Reactivity of Polyoxometalates have recently appeared. ... 

This misfolded form protease-resistant form (PrP ) or scrapie may form by... 

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]. 

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... 

Baron T, Crozet C, Biacabe AG, Philippe S, Verchere J, Bencsik A, Madec JY, Calavas D, Samarut J (2004) Molecular analysis of the protease-resistant prion protein in scrapie and bovine spongiform encephalopathy transmitted to ovine transgenic and wild-type mice. J Virol 78 6243-6251... 

Der Trab ist auch eine Krankheit der Schaafe, und ist ansteckend. Sie schleppen sich lange, verzehren sich nach und nach, und zuletzt miissen sie sterben. These sentences are taken from an article published in 1759 [1] and describe two hallmarks of prion diseases or transmissible spongiform encephalopathies (TSEs, summarized in Table 1) The formation and transmission of an infectious particle and the invariably fatal course of these diseases. More than 200 years later a landmark discovery paved the way to study the pathogenesis of prion diseases at a molecular level. Prusiner and colleagues reported the identification of a protease-resistant protein in brain extracts, which co-purified with the infectious scrapie agent [18]. After the N-terminal amino acid sequence of the proteinase K (PK)-resistant core of the prion protein (PrP 27-30) was published in 1984 [19], two... 

Caughey B, Raymond GJ, Ernst D et al (1991) N-Terminal truncation of the scrapie-associated form of PrP by lysosomal protease(s) implications regarding the site of conversion of PrP to the protease-resistant state. J Virol 65 6597-6603... 

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