title: Humanized knock-in mice expressing chimeric prion protein showed varied susceptibility to different human prions.
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 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.
authors: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yuzuru
authors: Y
authors: Taguchi
authors: Shirou
authors: S
authors: Mohri
authors: James W
authors: JW
authors: Ironside
authors: Tamaki
authors: T
authors: Muramoto
authors: Tetsuyuki
authors: T
authors: Kitamoto
mesh_terms: 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
chemical_list: D011328:Prions; D011993:Recombinant Fusion Proteins