RESEARCH ARTICLE Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie

Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative dis-eases affecting a wide range of mammalian species. They are caused by prions, a proteina-ceous pathogen essentially composed of PrPSc, an abnormal isoform of the host encoded cellular prion protein PrPC. Constrained steric interactions between PrPSc and PrPC are thought to provide prions with species specificity, and to control cross-species transmission into other host populations, including humans. Transgenetic expression of foreign PrP genes has been successfully and widely used to overcome the recognized resistance of mouse to foreign TSE sources. Rabbit is one of the species that exhibit a pronounced resis-tance to TSEs. Most attempts to infect experimentally rabbit have failed, except after inocu-lation with cell-free generated rabbit prions. To gain insights on the molecular determinants of the relative resistance of rabbits to prions, we generated transgenic rabbits expressin