Follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions.
Infectious prion diseases initiate infection within lymphoid organs where prion infectivity accumulates during the early stages of peripheral infection. In a mouse-adapted prion infection, an abnormal isoform (PrP(Sc)) of prion protein (PrP) accumulates in follicular dendritic cells within lymphoid organs. Human prions, however, did not cause an accumulation of PrP(Sc) in the wild type mice. Here, we report that knock-in mouse expressing humanized chimeric PrP demonstrated PrP(Sc) accumulations in follicular dendritic cells following human prion infections, including variant Creutzfeldt-Jakob disease. The accumulated PrP(Sc) consisted of recombinant PrP, but not of the inoculated human PrP. These accumulations were detectable in the spleens of all mice examined 30 days post-inoculation. Infectivity of the spleen was also evident. Conversion of humanized PrP in the spleen provides a rapid and sensitive bioassay method to uncover the infectivity of human prions. This model should facilitate the prevention of infectious prion diseases.
Kitamoto
Tetsuyuki
T
Department of Neurological Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Japan. kitamoto@mail.cc.tohoku.ac.jp
Mohri
Shirou
S
Ironside
James W
JW
Miyoshi
Ichiro
I
Tanaka
Tomoyuki
T
Kitamoto
Noritoshi
N
Itohara
Shigeyoshi
S
Kasai
Noriyuki
N
Katsuki
Motoya
M
Higuchi
Jun
J
Muramoto
Tamaki
T
Shin
Ryong-Woon
RW
D000818:Animals; D001681:Biological Assay / Q000379:methods*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis; D020566:Dendritic Cells, Follicular / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D018620:PrPSc Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D017096:Prion Diseases / Q000175:diagnosis* / Q000635:transmission; D011328:Prions / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000378:metabolism / Q000473:pathology
D018620:PrPSc Proteins; D011328:Prions; D011993:Recombinant Fusion Proteins