TY - JOUR
T1 - Humanized Knock-in Mice Expressing Chimeric Prion Protein Showed Varied Susceptibility to Different Human Prions
AU - Taguchi, Yuzuru
AU - Mohri, Shirou
AU - Ironside, James W.
AU - Muramoto, Tamaki
AU - Kitamoto, Tetsuyuki
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9440(10)63613-9
DO - 10.1016/S0002-9440(10)63613-9
M3 - Article
C2 - 14633630
AN - SCOPUS:0344844524
VL - 163
SP - 2585
EP - 2593
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 6
ER -