Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie.
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...
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2015-08-01
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doaj-b4546d4f5c7c4de3ae35e19c275034de2021-04-21T17:01:13ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-08-01118e100507710.1371/journal.ppat.1005077Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie.Pierre SarradinCéline VigliettaClaude LimouzinOlivier AndréolettiNathalie Daniel-CarlierCéline BarcMathieu Leroux-CoyauPatricia BerthonJérôme ChapuisChristelle RossignolJean-Luc GattiMaya BelghaziValérie LabasJean-Luc VilotteVincent BéringueFrédéric LantierHubert LaudeLouis-Marie HoudebineTransmissible 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.https://doi.org/10.1371/journal.ppat.1005077 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pierre Sarradin Céline Viglietta Claude Limouzin Olivier Andréoletti Nathalie Daniel-Carlier Céline Barc Mathieu Leroux-Coyau Patricia Berthon Jérôme Chapuis Christelle Rossignol Jean-Luc Gatti Maya Belghazi Valérie Labas Jean-Luc Vilotte Vincent Béringue Frédéric Lantier Hubert Laude Louis-Marie Houdebine |
spellingShingle |
Pierre Sarradin Céline Viglietta Claude Limouzin Olivier Andréoletti Nathalie Daniel-Carlier Céline Barc Mathieu Leroux-Coyau Patricia Berthon Jérôme Chapuis Christelle Rossignol Jean-Luc Gatti Maya Belghazi Valérie Labas Jean-Luc Vilotte Vincent Béringue Frédéric Lantier Hubert Laude Louis-Marie Houdebine Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie. PLoS Pathogens |
author_facet |
Pierre Sarradin Céline Viglietta Claude Limouzin Olivier Andréoletti Nathalie Daniel-Carlier Céline Barc Mathieu Leroux-Coyau Patricia Berthon Jérôme Chapuis Christelle Rossignol Jean-Luc Gatti Maya Belghazi Valérie Labas Jean-Luc Vilotte Vincent Béringue Frédéric Lantier Hubert Laude Louis-Marie Houdebine |
author_sort |
Pierre Sarradin |
title |
Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie. |
title_short |
Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie. |
title_full |
Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie. |
title_fullStr |
Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie. |
title_full_unstemmed |
Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie. |
title_sort |
transgenic rabbits expressing ovine prp are susceptible to scrapie. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2015-08-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.ppat.1005077 |
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