The cerebral prion protein (PrP) isolated in the absence of proteinase K digestion, from ruminants prion sources transmitted to ovine transgenic mice, was studied by Western blot analysis. A C2 PrP fragment, showing strain-specific cleavages, similar to those observed after proteinase K or thermolysin digestion, accumulated in the brain. ‘CH1641-like’ scrapie was characterized by the unique accumulation of a more C-terminally cleaved PrP fragment (CTF14). A similar, protease-resistant, PrP product was observed after proteinase K or thermolysin digestion. Whereas classical BSE appeared highly resistant to thermolysin digestion, CH1641 and ‘CH1641-like’ natural isolates did not show any remarkable feature regarding resistance to thermolysin. Thus, the molecular strain-specific features in the brain of transmissible spongiform encephalopathy infected mice essentially reflect the PrP proteolytic processing occurring .


Article metrics loading...

Loading full text...

Full text loading...



  1. Baron, T. & Biacabe, A.-G.(2007). Molecular behaviors of “CH1641-like” sheep scrapie isolates in ovine transgenic mice (TgOvPrP4). J Virol 81, 7230–7237.[CrossRef] [Google Scholar]
  2. Baron, T., Crozet, C., Biacabe, A.-G., Philippe, S., Verchère, J., Bencsik, A., Madec, J. Y., 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.[CrossRef] [Google Scholar]
  3. Baron, T., Bencsik, A., Biacabe, A.-G., Morignat, A. & Bessen, R. A.(2007). Phenotypic similarity of transmissible mink encephalopathy in cattle and L-type bovine spongiform encephalopathy in a mouse model. Emerg Infect Dis 13, 1887–1894.[CrossRef] [Google Scholar]
  4. Baron, T., Bencsik, A., Vulin, J., Biacabe, A.-G., Morignat, E., Verchère, J. & Bétemps, D.(2008). A C-terminal protease-resistant prion fragment distinguishes ovine “CH1641-like” scrapie from bovine classical and L-type BSE in ovine transgenic mice. PLoS Pathog 4, e1000137[CrossRef] [Google Scholar]
  5. Biacabe, A.-G., Jacobs, J. G., Bencsik, A., Langeveld, J. P. & Baron, T.(2007). H-type bovine spongiform encephalopathy: complex molecular features and similarities with human prion diseases. Prion 1, 61–68.[CrossRef] [Google Scholar]
  6. Bocharova, O. V., Breydo, L., Salnikov, V. V., Gill, A. C. & Baskalov, I. V.(2005). Synthetic prions generated in vitro are similar to a newly identified subpopulation of PrPSc from sporadic Creutzfeldt–Jakob disease. Protein Sci 14, 1222–1232.[CrossRef] [Google Scholar]
  7. Chen, S. G., Teplow, D. B., Parchi, P., Teller, J. K., Gambetti, P. & Autilio-Gambetti, L.(1995). Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem 270, 19173–19180.[CrossRef] [Google Scholar]
  8. Cronier, S., Gros, N., Tattum, M. H., Jackson, G. S., Clarke, A. R., Collinge, J. & Wadsworth, J. D.(2008). Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysin. Biochem J 416, 297–305.[CrossRef] [Google Scholar]
  9. Hope, J., Wood, S. C. E. R., Birkett, C. R., Chong, A., Bruce, M. E., Cairns, D., Goldmann, W., Hunter, N. & Bostock, C. J.(1999). Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641. J Gen Virol 80, 1–4. [Google Scholar]
  10. Jeffrey, M., Martin, S. & Gonzalez, L.(2003). Cell-associated variants of disease-specific prion protein immunolabelling are found in different sources of sheep transmissible spongiform encephalopathy. J Gen Virol 84, 1033–1045.[CrossRef] [Google Scholar]
  11. Jeffrey, M., Gonzalez, L., Chong, A., Foster, J., Goldmann, W., Hunter, N. & Martin, S.(2006). Ovine infection with the agents of scrapie (CH1641 isolate) and bovine spongiform encephalopathy: immunochemical similarities can be resolved by immunohistochemistry. J Comp Pathol 134, 17–29.[CrossRef] [Google Scholar]
  12. Jiménez-Huete, A., Lievens, P. M. J., Vidal, R., Piccardo, P., Ghetti, B., Tagliavini, F., Frangione, B. & Prelli, F.(1998). Endogenous proteolytic cleavage of normal and disease-associated isoforms of the human prion protein in neural and non-neural tissues. Am J Pathol 153, 1561–1572.[CrossRef] [Google Scholar]
  13. Mangé, A., Béranger, F., Peoc’h, K., Onodera, T., Frobert, Y. & Lehmann, S.(2004). Alpha- and beta-cleavages of the amino-terminus of the cellular prion protein. Biol Cell 96, 125–132.[CrossRef] [Google Scholar]
  14. Notari, S., Strammiello, R., Capellari, S., Giese, A., Cescatti, M., Grassi, J., Ghetti, B., Langeveld, J. P., Zou, W. Q. & other authors(2008). Characterization of truncated forms of abnormal prion protein in Creutzfeldt–Jakob disease. J Biol Chem 283, 30557–30565.[CrossRef] [Google Scholar]
  15. Owen, J. P., Maddison, B. C., Whitelam, G. C. & Gough, K. C.(2007a). Use of thermolysin in the diagnosis of prion diseases. Mol Biotechnol 35, 161–170.[CrossRef] [Google Scholar]
  16. Owen, J. P., Rees, H. C., Maddison, B. C., Terry, L. A., Thorne, L., Jackman, R., Whitelam, G. C. & Gough, K. C.(2007b). Molecular profiling of ovine prion diseases by using thermolysin-resistant PrPSc and endogenous C2 PrP fragments. J Virol 81, 10532–10539.[CrossRef] [Google Scholar]
  17. Parchi, P., Zou, W., Wang, W., Brown, P., Capellari, S., Ghetti, B., Kopp, N., Schulz-Schaeffer, W. J., Kretzschmar, H. A. & other authors(2000). Genetic influence on the structural variations of the abnormal prion protein. Proc Natl Acad Sci U S A 97, 10168–10172.[CrossRef] [Google Scholar]
  18. Simon, S., Nugier, J., Morel, N., Boutal, H., Créminon, C., Benestad, S., Andréoletti, O., Lantier, F., Bilheude, J. M. & other authors(2008). Rapid typing of transmissible spongiform encephalopathy strains with differential ELISA. Emerg Infect Dis 14, 608–616.[CrossRef] [Google Scholar]
  19. Telling, G. C., Parchi, P., DeArmond, S. J., Cortelli, P., Montagna, P., Gabizon, R., Mastrianni, J., Lugaresi, E., Gambetti, P. & Prusiner, S. B.(1996). Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science 274, 2079–2082.[CrossRef] [Google Scholar]
  20. Yadavalli, R., Guttmann, R. P., Seward, T., Centers, A. P., Williamson, R. A. & Telling, G. C.(2004). Calpain-dependent endoproteolytic cleavage of PrPSc modulates scrapie prion propagation. J Biol Chem 279, 21948–21956.[CrossRef] [Google Scholar]
  21. Zou, W. Q., Capellari, S., Parchi, P., Sy, M. S., Gambetti, P. & Chen, S. G.(2003). Identification of novel proteinase K-resistant C-terminal fragments of PrP in Creutzfeldt–Jakob disease. J Biol Chem 278, 40429–40436.[CrossRef] [Google Scholar]

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error