Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein

Glenn C. Telling, Michael Scott, Karen K. Hsiao, Dallas Foster, Shu Lian Yang, Marilyn Torchia, Katie C.L. Sidle, John Collinge, Stephen J. Dearmond, Stanley B. Prusiner

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246 Scopus citations

Abstract

Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease ≃200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrP(Sc) (where PrP(Sc) is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrP(Sc). The patterns of MHu2MPrP(Sc) and MoPrP(Sc) accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease >500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.

Original languageEnglish (US)
Pages (from-to)9936-9940
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number21
DOIs
StatePublished - Oct 11 1994

Keywords

  • bovine spongiform encephalopathy
  • human growth hormone
  • prion propagation
  • scrapie
  • species barrier

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