Abstract / Description of output
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.
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 language | English |
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Title of host publication | Prion 2006 Abstracts |
Pages | 155-155 |
Publication status | Published - 2006 |
Event | Prion 2006 - Turin, Italy Duration: 4 Oct 2006 → 6 Oct 2006 |
Conference
Conference | Prion 2006 |
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Country/Territory | Italy |
City | Turin |
Period | 4/10/06 → 6/10/06 |