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Updated: Jul 16, 2026
Protein Misfolding Cyclic Amplification of Prions
Published on: November 7, 2012
Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes
Abstract:
Transgenic mice expressing chimeric prion protein (PrP) genes derived from Syrian hamster (SHa) and mouse (Mo) PrP genes were constructed. One SHa/MoPrP gene, designated MH2M PrP, contains five amino acid substitutions encoded by SHaPrP, while another construct, designated MHM2 PrP, has two substitutions. Transgenic (Tg) (MH2M PrP) mice were susceptible to both Syrian hamster and mouse prions, whereas three lines expressing MHM2 PrP were resistant to Syrian hamster prions. The brains of Tg(MH2M PrP) mice dying of scrapie contained chimeric PrPSc and prions with an artificial host range favoring propagation in mice that express the corresponding chimeric PrP and were also transmissible, at reduced efficiency, to nontransgenic mice and hamsters. Our findings provide genetic evidence for homophilic interactions between PrPSc in the inoculum and PrPc synthesized by the host.
Insights
Transgenic mice with chimeric prion protein (PrP) genes showed altered susceptibility to prion diseases. These findings suggest that the host
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Prion diseases are fatal neurodegenerative disorders.
- Prion protein (PrP) misfolding and aggregation are central to pathogenesis.
- Understanding PrP interactions is crucial for developing therapeutics.
Purpose of the Study:
- To investigate the role of specific prion protein (PrP) gene sequences in prion disease susceptibility.
- To determine if chimeric PrP genes influence prion propagation and host range.
- To provide genetic evidence for homophilic interactions in prion pathogenesis.
Main Methods:
- Construction of transgenic mice expressing chimeric Syrian hamster (SHa)/mouse (Mo) PrP genes (MH2M PrP and MHM2 PrP).
- Inoculation of transgenic mice with SHa and Mo prions.
- Analysis of prionSc (scrapie form) and PrPc (cellular form) in infected mouse brains.
Main Results:
- Transgenic mice expressing MH2M PrP were susceptible to both SHa and Mo prions.
- Mice expressing MHM2 PrP were resistant to SHa prions.
- Infected MH2M PrP mice brains contained chimeric PrPSc and prions with an altered host range favoring chimeric PrP expression.
Conclusions:
- Genetic evidence supports homophilic interactions between PrPSc and host PrPc.
- Chimeric PrP genes can create artificial prion host ranges.
- Prion propagation is influenced by specific amino acid sequences in the host PrP.
