Queen Margaret University logo
    • Login
    View Item 
    •   QMU Repositories
    • eResearch
    • School of Health Sciences
    • Dietetics, Nutrition and Biological Sciences
    • View Item
    •   QMU Repositories
    • eResearch
    • School of Health Sciences
    • Dietetics, Nutrition and Biological Sciences
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    The role of host PrP in control of incubation time

    Date
    2005
    Author
    Manson, Jean C.
    Barron, Rona
    Hart, Patricia
    Tuzi, Nadia L.
    Bishop, Matthew T.
    Metadata
    Show full item record
    Citation
    Manson, J., Barron, R., Hart, P., Tuzi, N., Bishop, M. (2005). The role of host PrP in control of incubation time. In: Kitamoto, T. (eds) Prions. Springer, Tokyo. https://doi.org/10.1007/4-431-29402-3_9
    Abstract
    PrP is central to TSE disease and has been hypothesised to be the infectious agent. Polymorphisms in the PrP gene are associated with different incubation times of disease following exposure to an infectious agent and mutations in the human PrP gene can apparently lead to spontaneous genetic disease. Strains of TSE agent are proposed to be generated and maintained through differences in glycosylation or conformation of PrP and the barrier to infection between species is thought to be due to the differences in the sequence of PrP between different species. To test these hypotheses, we have introduced specific modifications into the endogenous mouse Prnp gene by gene targeting. The mutated PrP gene is in the correct location under the control of the endogenous Prnp regulatory sequences and thus expressed in the same tissues and amounts as the wild type Prnp gene. By altering the murine PrP coding region to that of another species we have established that increasing overall identity between host and donor PrP can lead to either an increase or a decrease in incubation time of disease in a strain dependent manner. We have introduced a point mutation (101L) into the N-terminus of the host PrP and shown that it dramatically changes the susceptibility of the host to infection from different species. We have in addition demonstrated that polymorphisms in the N terminus (L108T) and C-terminus (F189V) of host PrP both alter the incubation time of disease. We have in addition introduced mutations into the Prnp gene which prevent glycosylation at each or both of the two N-linked glycosylation sites of PrP. Inoculation of these mice with infectivity has established that glycosylation of host PrP can influence incubation time of disease, vacuolar pathology and strain determination.
    URI
    https://eresearch.qmu.ac.uk/handle/20.500.12289/12735
    Official URL
    https://doi.org/10.1007/4-431-29402-3_9
    Collections
    • Dietetics, Nutrition and Biological Sciences

    Queen Margaret University: Research Repositories
    Accessibility Statement | Repository Policies | Contact Us | Send Feedback | HTML Sitemap

     

    Browse

    All QMU RepositoriesCommunities & CollectionsBy YearBy PersonBy TitleBy QMU AuthorBy Research CentreThis CollectionBy YearBy PersonBy TitleBy QMU AuthorBy Research Centre

    My Account

    LoginRegister

    Queen Margaret University: Research Repositories
    Accessibility Statement | Repository Policies | Contact Us | Send Feedback | HTML Sitemap