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    Transmission of murine scrapie to P101L transgenic mice

    Date
    2003-11-01
    Author
    Barron, Rona
    Thomson, Val
    King, Declan
    Melton, David W.
    Manson, Jean C.
    Metadata
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    Citation
    Barron, R.M., Thomson, V., King, D., Shaw, J., Melton, D.W. and Manson, J.C. (2003) ‘Transmission of murine scrapie to P101L transgenic mice’, Journal of General Virology, 84(11), pp. 3165–3172. Available at: https://doi.org/10.1099/vir.0.19147-0.
    Abstract
    The PrP protein is central to the transmissible spongiform encephalopathies (TSEs), and the amino acid sequence of this protein in the host can influence both incubation time of disease and targeting of disease pathology. The N terminus of murine PrP has been proposed to be important in the replication of TSE agents, as mutations or deletions in that region can alter the efficiency of agent replication. To address this hypothesis and to investigate the mechanisms by which host PrP sequence controls the outcome of disease, we have assessed the influence of a single amino acid alteration in the N-terminal region of murine PrP (P101L) on the transmission of TSE agents between mice. Mice homozygous for the mutation (101LL) were inoculated with TSE strains 139A and 79A derived from mice carrying a Prnpa allele, and 79V and 301V derived from mice carrying a Prnpb allele. Incubation times in 101LL mice were extended with all four strains of agent when compared with those in the corresponding mouse genotype from which the infectivity was derived. However, the degree to which the incubation period was increased showed considerable variation between each strain of agent. Moreover, the presence of this single amino acid alteration resulted in a 70 day reduction in incubation time of the 301V strain in Prnpa mice. The effect of the 101L mutation on murine scrapie incubation time appears therefore to be strain specific.
    URI
    https://eresearch.qmu.ac.uk/handle/20.500.12289/12726
    Official URL
    https://doi.org/10.1099/vir.0.19147-0
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    • Dietetics, Nutrition and Biological Sciences

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