Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie

PLoS Pathogens

Frédéric Lantier¹  Hubert Laude¹  Patricia Berthon²  Céline Viglietta²  Olivier Andréoletti²  Vincent Béringue³  Jean-Luc Vilotte³  Louis-Marie Houdebine⁴  Jean-Luc Gatti⁵  Valérie Labas⁶  Céline Barc⁷  Jérôme Chapuis⁷  Claude Limouzin⁷  Mathieu Leroux-Coyau⁸  Pierre Sarradin⁸  Christelle Rossignol⁸  Maya Belghazi⁸  Nathalie Daniel-Carlier⁹ 

[1]CNRS-Aix-Marseille Université, UMR7286, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, CRN2M, Marseille, France

[2]INRA, UE1277, Plate-Forme d’Infectiologie Expérimentale, PFIE, Nouzilly, France

[3]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

[4]INRA, UMR1313, Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France

[5]INRA, UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France

[6]INRA- CNRS-UNS, UMR1355, Institut Sophia Agrobiotech, ISA, Sophia Antipolis, France

[7]INRA-CNRS-ENVA, UMR1198, Biologie du Développement et Reproduction, BDR, Jouy-en-Josas, France

[8]INRA-Université de Tours, UMR1282, Infectiologie et Santé Publique, ISP, Nouzilly, France

[9]UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Toulouse, France

关键词: Rabbits;    Animal prion diseases;    Prions;    Scrapie;    Genetically modified animals;    Sheep;    Veterinary diseases;    Brain diseases;   

DOI  :  10.1371/journal.ppat.1005077

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY