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Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system
S Brandner1, A Raeber, A Sailer
1Institute of Neuropathology, University Hospital, Zürich, Switzerland.
Summary
Mice lacking prion protein (PrPC) resist scrapie. Introducing PrPC-expressing cells into these mice did not permit prion spread, demonstrating PrPC is essential for prion propagation along neural pathways.
Area of Science:
- Neuroscience
- Infectious Diseases
- Molecular Biology
Background:
- Prion diseases, like scrapie, are neurodegenerative disorders.
- The cellular prion protein (PrPC) is implicated in prion propagation.
- Mice lacking PrPC (Prnp%) are resistant to scrapie.
Purpose of the Study:
- To investigate the role of PrPC in the spread of scrapie prions.
- To determine if PrPC is necessary for prion propagation along neural pathways.
Main Methods:
- Intraocular inoculation of scrapie prions into Prnp% mice with PrP-overexpressing neurografts.
- Utilizing immunotolerant Prnp% mice engrafted with PrP-producing tissue to control for immune responses.
- Monitoring for scrapie-specific pathology and protease-resistant PrP (PrPSc) accumulation.
Main Results:
- Prnp% mice lacking PrPC are resistant to scrapie infection.
- PrP-expressing neurografts in Prnp% brains allowed prion replication.
- Intraocular prion inoculation did not lead to disease in Prnp% mice, even with PrP-expressing grafts, suggesting PrPC is required for spread.
- Immune responses did not interfere with the observed resistance in Prnp% mice.
Conclusions:
- PrPC is essential for the spread of scrapie prions.
- Prion propagation along neural pathways is dependent on the presence of PrPC.
- These findings highlight PrPC as a critical factor in prion pathogenesis and neuroinvasion.