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

Michael R. Scott, Jiri Safar, Glenn Telling, Oanh Nguyen, Darlene Groth, Marilyn Torchia, Ruth Koehler, Patrick Tremblay, Dirk Walther, Fred E. Cohen, Stephen J. DeArmond, Stanley B. Prusiner

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14279-14284
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number26
DOIs
StatePublished - Dec 23 1997

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Bovine Spongiform Encephalopathy
Prions
Transgenic Mice
Epitopes
Transgenes
Creutzfeldt-Jakob Syndrome
Gliosis
Prion Proteins
Brain Stem

Keywords

  • Bioassays
  • Creutzfeldt-Jakob disease
  • Transgenics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice. / Scott, Michael R.; Safar, Jiri; Telling, Glenn; Nguyen, Oanh; Groth, Darlene; Torchia, Marilyn; Koehler, Ruth; Tremblay, Patrick; Walther, Dirk; Cohen, Fred E.; DeArmond, Stephen J.; Prusiner, Stanley B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 26, 23.12.1997, p. 14279-14284.

Research output: Contribution to journalArticle

Scott, MR, Safar, J, Telling, G, Nguyen, O, Groth, D, Torchia, M, Koehler, R, Tremblay, P, Walther, D, Cohen, FE, DeArmond, SJ & Prusiner, SB 1997, 'Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice', Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 26, pp. 14279-14284. https://doi.org/10.1073/pnas.94.26.14279
Scott, Michael R. ; Safar, Jiri ; Telling, Glenn ; Nguyen, Oanh ; Groth, Darlene ; Torchia, Marilyn ; Koehler, Ruth ; Tremblay, Patrick ; Walther, Dirk ; Cohen, Fred E. ; DeArmond, Stephen J. ; Prusiner, Stanley B. / Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 26. pp. 14279-14284.
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