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    Changing a single amino acid in the N-terminus of murine PrP alters incubation time across three species barriers

    Date
    2001-09-17
    Author
    Barron, Rona
    Thomson, Val
    Jamieson, Elizabeth
    Melton, David W.
    Ironside, James
    Will, Robert
    Manson, Jean C.
    Metadata
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    Citation
    Barron, R.M., Thomson, V., Jamieson, E., Melton, D.W., Ironside, J., Will, R. and Manson, J.C. (2001) ‘Changing a single amino acid in the N-terminus of murine PrP alters TSE incubation time across three species barriers’, The EMBO Journal, 20(18), pp. 5070–5078. Available at: https://doi.org/10.1093/emboj/20.18.5070.
    Abstract
    The PrP gene of the host exerts a major influence over the outcome of transmissible spongiform encephalopathy (TSE) disease, but the mechanism by which this is achieved is not understood. We have introduced a specific mutation into the endogenous murine PrP gene using gene targeting to produce transgenic mice with a single amino acid alteration (proline to leucine) at amino acid position 101 in their PrP protein (P101L). The effect of this alteration on incubation time, targeting and PrPSc formation has been studied in TSE-infected animals. Transgenic mice carrying the P101L mutation in PrP have remarkable differences in incubation time and targeting of central nervous system pathology compared with wild-type littermates, following inoculation with infectivity from human, hamster, sheep and murine sources. This single mutation can alter incubation time across three species barriers in a strain-dependent manner. These findings suggest a critical role for the structurally ‘flexible’ region of PrP in agent replication and targeting of TSE pathology.
    URI
    https://eresearch.qmu.ac.uk/handle/20.500.12289/12727
    Official URL
    https://doi.org/10.1093/emboj/20.18.5070
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    • Dietetics, Nutrition and Biological Sciences

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