Abstract
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.
Original language | English |
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Pages (from-to) | 280-6 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 294 |
Issue number | 2 |
DOIs | |
Publication status | Published - 7 Jun 2002 |
Keywords / Materials (for Non-textual outputs)
- Animals
- Biological Assay
- Brain
- Creutzfeldt-Jakob Syndrome
- Dendritic Cells, Follicular
- Disease Models, Animal
- Genetic Predisposition to Disease
- Humans
- Immunohistochemistry
- Mice
- Mice, Transgenic
- PrPSc Proteins
- Prion Diseases
- Prions
- Recombinant Fusion Proteins
- Spleen