Humanized knock-in mice expressing chimeric prion protein showed varied susceptibility to different human prions.
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 approximately 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.
Taguchi
Yuzuru
Y
Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
Mohri
Shirou
S
Ironside
James W
JW
Muramoto
Tamaki
T
Kitamoto
Tetsuyuki
T
D000818:Animals; D001921:Brain / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004388:Dura Mater / Q000637:transplantation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007049:Iatrogenic Disease; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D058225:Plaque, Amyloid / Q000473:pathology; D011328:Prions / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D013997:Time Factors; D016378:Tissue Transplantation / Q000009:adverse effects
D011328:Prions; D011993:Recombinant Fusion Proteins