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Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice

Scott, M.R., Safar, J., Telling, G., Nguyen, O., Groth, D., Torchia, M., Koehler, R., Tremblay, P., Walther, D., Cohen, F.E.
Proceedings of the National Academy of Sciences of the United States of America 1997 v.94 no.26 pp. 14279-14284
pathological processes and conditions, mice, prions, bovine spongiform encephalopathy, disease transmission, animal proteins, cattle, gene transfer, gene expression, pathogenesis, epitopes, immunohistochemistry, brain, extracts, biological resistance
There is considerable concern that bovine prions from cattle with bovine spongiform encephalopathy (BSE) may have been passed to humans (Hu), resulting in a new form of Creutzfeldt-Jakob disease (CJD). We report here the transmission of bovine (Bo) prions to transgenic (Tg) mice expressing BoPrP; one Tg line exhibited incubation times of approximately 200 days. Like most cattle with BSE, vacuolation and astrocytic gliosis were confined in the brainstems of these Tg mice. Unexpectedly, mice expressing a chimeric Bo/Mo PrP transgene were resistant to BSE prions whereas mice expressing Hu or Hu/Mo PrP transgenes were susceptible to Hu priors. A comparison of differences in Mo, Bo, and Hu residues within the C terminus of PrP defines an epitope that modulates conversion of prp(C) into PrP(Sc) and, as such, controls prion transmission across species. Development of susceptible Tg(BoPrP) mice provides a means of measuring bovine prions that may prove critical in minimizing future human exposure.