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PrP-deficient mice are resistant to scrapie
C Weissmann1, H Büeler, M Fischer
1Institut für Molekularbiologie I, Universität Zürich, Switzerland.
Annals of the New York Academy of Sciences
|June 6, 1994
Summary
Mice lacking the normal prion protein (PrPC) resisted scrapie infection, demonstrating its necessity for disease susceptibility. Introducing foreign prion genes further highlighted the role of PrPC homology in prion disease.
Area of Science:
- Neuroscience
- Molecular Biology
- Infectious Diseases
Background:
- Prions are infectious agents composed of misfolded prion proteins (PrPSc).
- The normal cellular prion protein (PrPC) is encoded by the host gene.
- The role of PrPC in prion disease pathogenesis has been investigated.
Purpose of the Study:
- To investigate the role of PrPC in susceptibility to prion diseases.
- To determine if PrPC is essential for prion propagation.
- To examine the effect of PrPC homology on prion disease.
Main Methods:
- Generation of PrPC-deficient (Prn-p0/0) and heterozygous (Prn-p0/+) mice.
- Inoculation of these mice with mouse-adapted scrapie prions.
- Introduction of Syrian hamster PrP transgenes into Prn-p0/0 mice.
- Assessment of scrapie symptoms and prion infectivity propagation.
Main Results:
- Prn-p0/0 mice showed normal development and behavior, and were highly resistant to mouse scrapie.
- Scrapie infectivity propagation in Prn-p0/0 mice was significantly reduced compared to wild-type controls.
- Heterozygous Prn-p0/+ mice exhibited enhanced resistance to scrapie.
- Prn-p0/0 mice expressing Syrian hamster PrP became susceptible to hamster prions but not mouse prions.
Conclusions:
- PrPC is essential for normal susceptibility to prion diseases like scrapie.
- Lack of homology between the infectious prion and host PrP significantly retards disease.
- These findings support the prion hypothesis and highlight the importance of PrPC in disease