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Communication dans un congrès

Investigating natural scrapie strain diversity in ovine PrP transgenic mice

Abstract : Serial transmission to a panel of congenic mouse lines, where characteristics of incubation time and brain vacuolation areas give distinct patterns, is the current way of investigating strain biological diversity in natural sheep scrapie. Following inoculation of natural scrapie isolates to mice, the disease commonly requires 1 or 2 years to develop, and a proportion of isolates fail to be transmitted. As a consequence, a limited number of isolates have been studied yet, and the extent of the natural scrapie strain variation remains largely unexplored. In an effort to develop an improved model for transmission of sheep scrapie, we have expanded a series of transgenic mice (tgOv) that express the VRQ (Val136-Arg154-Gln171) allele of ovine PrP on a null mouse PrP background. This allele is associated with the highest susceptibility to the disease in many flocks. Mice of the tgOv line tg338, expressing high PrP level (~ 10-fold that in sheep brain), were inoculated intracerebrally with more than 40 scrapie sources including sheep of distinct PrP genotypes and of various geographical areas in Europe. In contrast with earlier studies using non-transgenic mice, all isolates transmitted successfully, generally with a ~ 100% attack rate. However, the incubation time to death differed widely among the isolates, ranging from 70 to 750 days. More than half of the isolates transmitted in <= 200 days post-inoculation. No correlation was found between the donor PrP genotype and the transmission efficiency. The isolates were found to distribute in distinct groups according to the molecular signature of brain PrPsc and the survival time on secondary passage, and all differed from BSE agent experimentally transmitted to sheep. Altogether these results argue that tgOv mice overexpressing the VRQ allele may provide a valuable alternative to conventional mice for field scrapie strain characterisation.
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Communication dans un congrès
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https://hal.inrae.fr/hal-02760243
Déposant : Migration Prodinra <>
Soumis le : jeudi 4 juin 2020 - 04:58:51
Dernière modification le : vendredi 12 juin 2020 - 10:43:26

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  • HAL Id : hal-02760243, version 1
  • PRODINRA : 144463

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Annick Le Dur, Thanh Lan Lai-Thi, Nathalie Besnard, Aude Laisné, Gaëlle Tilly, et al.. Investigating natural scrapie strain diversity in ovine PrP transgenic mice. Prion 2004, May 2004, Paris, France. ⟨hal-02760243⟩

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