Transmission and characterization of bovine spongiform encephalopathy sources in two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59)

C Cordier, A Bencsik, S Philippe, D Bétemps, F Ronzon, D Calavas, C Crozet, T Baron
Journal of General Virology 2006, 87: 3763-71
Transgenic mice expressing the prion protein (PrP) of species affected by transmissible spongiform encephalopathies (TSEs) have recently been produced to facilitate experimental transmission of these diseases by comparison with wild-type mice. However, whilst wild-type mice have largely been described for the discrimination of different TSE strains, including differentiation of agents involved in bovine spongiform encephalopathy (BSE) and scrapie, this has been only poorly described in transgenic mice. Here, two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59), expressing the ovine PrP (A136 R154 Q171) under control of the neuron-specific enolase promoter, were studied; they were challenged with brainstem or spinal cord from experimentally BSE-infected sheep (AA136 RR154 QQ171 and AA136 RR154 RR171 genotypes) or brainstem from cattle BSE and natural sheep scrapie. The disease was transmitted successfully from all of these sources, with a mean of approximately 300 days survival following challenge with material from two ARQ-homozygous BSE-infected sheep in TgOvPrP4 mice, whereas the survival period in mice challenged with material from the ARR-homozygous BSE-infected sheep was 423 days on average. It was shown that, in the two ovine transgenic mouse lines, the Western blot characteristics of protease-resistant PrP (PrP(res)) were similar, whatever the BSE source, with a low apparent molecular mass of the unglycosylated glycoform, a poor labelling by P4 monoclonal antibody and high proportions of the diglycosylated form. With all BSE sources, but not with scrapie, florid plaques were observed in the brains of mice from both transgenic lines. These data reinforce the potential of this recently developed experimental model for the discrimination of BSE from scrapie agents.

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