TY - JOUR
T1 - Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice
AU - Scott, Michael R.
AU - Safar, Jiri
AU - Telling, Glenn
AU - Nguyen, Oanh
AU - Groth, Darlene
AU - Torchia, Marilyn
AU - Koehler, Ruth
AU - Tremblay, Patrick
AU - Walther, Dirk
AU - Cohen, Fred E.
AU - DeArmond, Stephen J.
AU - Prusiner, Stanley B.
PY - 1997/12/23
Y1 - 1997/12/23
N2 - 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 ≃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 prions. 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.
AB - 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 ≃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 prions. 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.
KW - Bioassays
KW - Creutzfeldt-Jakob disease
KW - Transgenics
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U2 - 10.1073/pnas.94.26.14279
DO - 10.1073/pnas.94.26.14279
M3 - Article
C2 - 9405603
AN - SCOPUS:13144275223
SN - 0027-8424
VL - 94
SP - 14279
EP - 14284
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 26
ER -