title: Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie.
abstract: Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting a wide range of mammalian species. They are caused by prions, a proteinaceous 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 resistance to TSEs. Most attempts to infect experimentally rabbit have failed, except after inoculation 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 expressing the susceptible V136R154Q171 allele of the ovine PRNP gene on a rabbit wild type PRNP New Zealand background and assessed their experimental susceptibility to scrapie prions. All transgenic animals developed a typical TSE 6-8 months after intracerebral inoculation, whereas wild type rabbits remained healthy more than 700 days after inoculation. Despite the endogenous presence of rabbit PrPC, only ovine PrPSc was detectable in the brains of diseased animals. Collectively these data indicate that the low susceptibility of rabbits to prion infection is not enciphered within their non-PrP genetic background.
authors.affiliation: INRA-Université de Tours, UMR1282, Infectiologie et Santé Publique, ISP, Nouzilly, France; INRA, UE1277, Plate-Forme d'Infectiologie Expérimentale, PFIE, Nouzilly, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarradin
authors.affiliation: INRA-CNRS-ENVA, UMR1198, Biologie du Développement et Reproduction, BDR, Jouy-en-Josas, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Viglietta
authors.affiliation: INRA, UE1277, Plate-Forme d'Infectiologie Expérimentale, PFIE, Nouzilly, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Limouzin
authors.affiliation: UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
authors.affiliation: INRA-CNRS-ENVA, UMR1198, Biologie du Développement et Reproduction, BDR, Jouy-en-Josas, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Daniel-Carlier
authors.affiliation: INRA-Université de Tours, UMR1282, Infectiologie et Santé Publique, ISP, Nouzilly, France; INRA, UE1277, Plate-Forme d'Infectiologie Expérimentale, PFIE, Nouzilly, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Barc
authors.affiliation: INRA-CNRS-ENVA, UMR1198, Biologie du Développement et Reproduction, BDR, Jouy-en-Josas, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Leroux-Coyau
authors.affiliation: INRA-Université de Tours, UMR1282, Infectiologie et Santé Publique, ISP, Nouzilly, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Berthon
authors.affiliation: INRA, UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Chapuis
authors.affiliation: INRA-Université de Tours, UMR1282, Infectiologie et Santé Publique, ISP, Nouzilly, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Rossignol
authors.affiliation: INRA- CNRS-UNS, UMR1355, Institut Sophia Agrobiotech, ISA, Sophia Antipolis, France; INRA, UMR INRA85, UMR CNRS 7247, Université de Tours, Institut Français du Cheval et de l'Equitation, Physiologie de la Reproduction et des Comportements, Plate-forme d'Analyse Intégrative des Biomolécules, Nouzilly, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Gatti
authors.affiliation: INRA, UMR INRA85, UMR CNRS 7247, Université de Tours, Institut Français du Cheval et de l'Equitation, Physiologie de la Reproduction et des Comportements, Plate-forme d'Analyse Intégrative des Biomolécules, Nouzilly, France; CNRS-Aix-Marseille Université, UMR7286, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, CRN2M, Marseille, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Belghazi
authors.affiliation: CNRS-Aix-Marseille Université, UMR7286, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, CRN2M, Marseille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Labas
authors.affiliation: INRA, UMR1313, Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vilotte
authors.affiliation: INRA, UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
authors.affiliation: INRA-Université de Tours, UMR1282, Infectiologie et Santé Publique, ISP, Nouzilly, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lantier
authors.affiliation: INRA, UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
authors.affiliation: INRA-CNRS-ENVA, UMR1198, Biologie du Développement et Reproduction, BDR, Jouy-en-Josas, France.
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Houdebine
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D005260:Female; D015151:Immunoblotting; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D018621:PrPC Proteins / Q000235:genetics*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012608:Scrapie / Q000235:genetics*; D012756:Sheep; D013045:Species Specificity
chemical_list: D018621:PrPC Proteins