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Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie.

Pierre Sarradin1, Céline Viglietta2, Claude Limouzin3

  • 1INRA-Université de Tours, UMR1282, Infectiologie et Santé Publique, ISP, Nouzilly, France; INRA, UE1277, Plate-Forme d'Infectiologie Expérimentale, PFIE, Nouzilly, France.

Plos Pathogens
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Summary

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases caused by prions. Transgenic rabbits expressing ovine prion protein developed TSEs, indicating rabbit resistance is not due to non-prion genetic factors.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Veterinary Medicine

Background:

  • Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases.
  • Prions, misfolded prion proteins (PrPSc), cause TSEs by interacting with normal cellular prion proteins (PrPC).
  • Rabbit species exhibit significant resistance to prion diseases, hindering research.

Purpose of the Study:

  • To investigate the molecular basis of rabbit resistance to prion diseases.
  • To determine if altering prion protein genotype can overcome this resistance.

Main Methods:

  • Generated transgenic rabbits expressing the susceptible ovine prion protein (PrP) allele (V136R154Q171).
  • Inoculated transgenic and wild-type rabbits intracerebrally with scrapie prions.
  • Monitored animals for TSE development and analyzed brain tissue for prion presence.

Main Results:

  • All transgenic rabbits developed TSEs within 6-8 months post-inoculation.
  • Wild-type rabbits remained healthy for over 700 days.
  • Only ovine PrPSc, not rabbit PrPC, was detected in the brains of diseased transgenic animals.

Conclusions:

  • Rabbit resistance to prion infection is not determined by non-prion genetic factors.
  • The prion protein gene (PRNP) genotype plays a crucial role in determining susceptibility to TSEs.
  • Transgenic models expressing susceptible PrP alleles can overcome species barriers for prion diseases.