Host PrP glycosylation influences the outcome of transmissible spongiform encephalopathy infection

Nadia L. Tuzi, Enrico Cancellotti, Herbert Baybutt, L Aitchison, Barry Bradford, Pedro Piccardo, Rona Barron, Patricia Hart, Christopher Plinston, Jean Manson

Research output: Chapter in Book/Report/Conference proceedingConference contribution


PrP possessed two potential sites for N-linked glycosylation which together with the complexity of the
added sugars allows for the generation of a very large number of different glycosylated forms of PrP.
Numerous prion or transmissible spongiform encephalopathy (TSE) strains exist, but to date the
underlying nature of these strains that gives rise to their different properties remains elusive.
However, it has been proposed that the variation in PrP molecules arising from differential
glycosylation may account for, or contribute to, the many TSE strains and their characteristics.
Therefore to investigate this possibility we have generated three lines of gene targeted transgenic
mice with mutations at the first (G1), second (G2) or both (G3) glycosylation sites thus preventing the
addition of N-linked glycans at these sites. By using the gene targeting approach we can ensure the
altered PrP gene is in the endogenous position in the genome and is thus under its normal control
elements thereby eliminating the complication of overexpression and/or ectopic expression. We have
established that despite differences in cellular location, mono and un-glycosylated PrP can support
both clinical and pathological disease, albeit with varying degrees of susceptibility, following TSE
challenge. Moreover different TSE agents have dramatically different requirements for glycosylation
of host PrP. We have also demonstrated that TSE strain characteristics can be modified when
passaged through hosts with altered PrP glycosylation. Therefore, we consider glycoform analysis
should be used with caution as a means of defining the TSE strain infecting the host.
Original languageEnglish
Title of host publicationPrion 2006 Abstracts
Publication statusPublished - 2006
EventPrion 2006 - Turin, Italy
Duration: 4 Oct 20066 Oct 2006


ConferencePrion 2006


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