Follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions

• Published in: Biochemical and biophysical research communications Vol. 294; no. 2; pp. 280 - 286
• Main Authors: Kitamoto, Tetsuyuki, Mohri, Shirou, Ironside, James W, Miyoshi, Ichiro, Tanaka, Tomoyuki, Kitamoto, Noritoshi, Itohara, Shigeyoshi, Kasai, Noriyuki, Katsuki, Motoya, Higuchi, Jun, Muramoto, Tamaki, Shin, Ryong-Woon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.06.2002
• Subjects: Animals; Biological Assay - methods; Brain - metabolism; Brain - pathology; Conversion; Creutzfeldt-Jakob Syndrome - diagnosis; Creuzfeldt–Jakob disease; Dendritic Cells, Follicular - metabolism; Dendritic Cells, Follicular - pathology; Disease Models, Animal; Follicular dendritic cell; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Knock-in mouse; Mice; Mice, Transgenic; Prion Diseases - diagnosis; Prion Diseases - transmission; Prion protein; Prions - analysis; Prions - biosynthesis; Prions - genetics; PrPSc Proteins - analysis; PrPSc Proteins - biosynthesis; PrPSc Proteins - genetics; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - genetics; Spleen - metabolism; Spleen - pathology; Creuzfeldt–Jakob disease; Knock-in mouse; Prion protein; Follicular dendritic cell; Conversion
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)00476-X

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.