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Updated: Sep 30, 2026
Monitoring Immune Cells Trafficking Fluorescent Prion Rods Hours after Intraperitoneal Infection
Published on: November 19, 2010
Follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions
Tetsuyuki Kitamoto1, Shirou Mohri, James W Ironside
1Department of Neurological Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Japan. kitamoto@mail.cc.tohoku.ac.jp
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.
Insights
New mice models expressing humanized prion protein (PrP) show PrP(Sc) accumulation in spleens after human prion infection. This breakthrough aids in detecting prion infectivity and preventing diseases.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Infectious prion diseases involve prion protein (PrP) accumulation in lymphoid organs.
- Prion protein scrapie (PrPSc) accumulation occurs in follicular dendritic cells during mouse prion infection.
- Wild-type mice do not accumulate PrPSc following human prion exposure.
Purpose of the Study:
- To develop a mouse model for studying human prion infections.
- To investigate PrPSc accumulation in response to human prions.
- To establish a sensitive bioassay for human prion infectivity.
Main Methods:
- Generation of knock-in mice expressing humanized chimeric PrP.
- Inoculation of mice with human prions, including variant Creutzfeldt-Jakob disease.
- Detection of PrPSc accumulation in spleen tissues 30 days post-inoculation.
Main Results:
- Humanized PrP mice showed PrPSc accumulation in splenic follicular dendritic cells after human prion infection.
- Accumulated PrPSc was derived from recombinant PrP, not the inoculated human PrP.
- Spleen infectivity was detected in all examined mice 30 days post-inoculation.
Conclusions:
- The humanized PrP mouse model effectively mimics human prion infection.
- PrPSc accumulation in the spleen serves as an indicator of prion infectivity.
- This model offers a rapid and sensitive bioassay for human prion detection, aiding disease prevention.
