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Chimeric elk/mouse prion proteins in transgenic mice
Gültekin Tamgüney1,2, Kurt Giles1,2, Abby Oehler3
1Department of Neurology, University of California, San Francisco, CA, USA.
The Journal of General Virology
|October 27, 2012
Summary
Researchers developed new transgenic mice to study chronic wasting disease (CWD) prions faster. Chimeric elk/mouse prion protein genes altered susceptibility, revealing key C-terminal residues influencing prion replication.
Area of Science:
- Neuroscience
- Prion Biology
- Transgenic Animal Models
Background:
- Chronic wasting disease (CWD) is a fatal prion disease affecting cervids.
- Current bioassays for CWD prions in transgenic (Tg) mice are slow, hindering research.
- Developing more susceptible Tg mouse models is crucial for CWD investigation.
Purpose of the Study:
- To create and characterize Tg mice with enhanced susceptibility to CWD prions.
- To investigate the role of specific prion protein (PrP) residues in prion disease susceptibility and replication.
Main Methods:
- Generated 12 Tg mouse lines expressing chimeric elk/mouse PrP constructs.
- Determined incubation times after intracerebral inoculation with RML scrapie and CWD prions.
- Analyzed the impact of specific PrP residue mutations on prion disease progression.
Main Results:
- One Tg mouse line (Elk3M(SNIVVK)) showed rapid incubation (<70 days) with RML prions.
- Full-length elk PrP Tg mice had prolonged incubation (>250 days) with RML prions.
- Chimeric mice showed varied susceptibility to CWD prions, with specific mutations conferring resistance or susceptibility.
Conclusions:
- C-terminal residues of PrP play a critical role in controlling prion susceptibility and replication.
- Chimeric elk/mouse PrP constructs can modulate incubation times and host range of prion diseases.
- These findings advance the development of sensitive Tg mouse models for prion disease research.
