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PrP expression level and sensitivity to prion infection.

Jean-Yves Douet1, Caroline Lacroux, Fabien Corbière

  • 1INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.

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Summary

Transgenic mouse models expressing prion protein (PrP) are common for prion disease research. This study found that PrP-overexpressing mice and sheep yield similar prion infectious titer measurements, validating these models for prion disease studies.

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Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Genetics

Background:

  • Transgenic mouse models overexpressing prion protein (PrP) are crucial for quantifying prion infectious titers.
  • Concerns exist regarding how transgene expression levels affect susceptibility and the biological relevance of these prion disease models.

Purpose of the Study:

  • To evaluate the impact of transgene expression levels on the biological relevance of prion protein (PrP)-overexpressing mouse models.
  • To compare infectious titer estimates between sheep and PrP-overexpressing mice using a sheep scrapie isolate.

Main Methods:

  • Endpoint titration of a sheep scrapie isolate.
  • Infection studies conducted in sheep and in mice genetically engineered to overexpress ovine PrP.

Main Results:

  • Endpoint titration yielded comparable estimates of infectious titer for the sheep scrapie isolate in both sheep and mice overexpressing ovine PrP.
  • This suggests that PrP transgene expression levels in mice do not significantly skew prion titer measurements.

Conclusions:

  • Mice overexpressing the ovine prion protein (PrP) are a biologically relevant model for measuring infectious titers of sheep scrapie.
  • The findings support the continued use of these transgenic models in prion disease research, enhancing the reliability of titer measurements.