Humanized Knock-in Mice Expressing Chimeric Prion Protein Showed Varied Susceptibility to Different Human Prions

Yuzuru Taguchi, Shirou Mohri, James W. Ironside, Tamaki Muramoto, Tetsuyuki Kitamoto

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Mice to which human prions efficiently transmit in short incubation periods are valuable not only as research tools of human prions but also as reliable diagnostic tools. We recently produced a line of knock-in mouse expressing a unique human-mouse chimeric PrP (Ki-ChM mouse), which has mouse-specific residues practically only at the C-terminal part after posttranslational modification, and here we attempted transmission of various human prions to assess the susceptibility profile of the mouse. Susceptibility varied considerably depending on prions inoculated: highly susceptible to MM1 and MV1 types of sporadic Creutzfeldt-Jakob disease (CJD), developing disease within ∼150 days, familial CJD with M232R mutation, and dura graft-associated CJD (dCJD) without amyloid plaque; less susceptible to MM2-type sporadic CJD and variant CJD, with some mice lacking any sign of transmission; and totally resistant to VV2 type sporadic CJD and dCJD with amyloid plaque. The rather short incubation time achieved by Ki-ChM mice suggests new approaches to produce mice that develop prion disease with very short incubation periods. We compared the characteristic susceptibility profile of Ki-ChM with those of other precedent transgenic mice and discussed, including the prospects in developing genetically engineered mice susceptible to human prions.

Original languageEnglish
Pages (from-to)2585-2593
Number of pages9
JournalAmerican Journal of Pathology
Volume163
Issue number6
DOIs
Publication statusPublished - 2003 Dec

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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