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Title: In vitro analysis of C-terminal mutations of the murine PrP gene
Author: Coleman, Michele
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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PrP undergoes three major post-translational changes, N-terminal cleavage, N-linked glycosylation and the cleavage of a C-terminal peptide with the subsequent addition of a phosphatidylinositolglycolpipid (GPI-anchor), which is responsible for the protein's attachment to the membrane (ref, Stahl 1987). Most PrPsc appears to have an intact GPI-anchor although it cannot be released from tissue culture cells by the action of PIPLC as the wild-type can (Stahl 1990). However, 15% of PrPsc from hamster brain has been shown to be truncated at amino acid 228, these proteins having no GPI-anchor (Stahl 1990). The significance of these truncated proteins has not yet been elucidated. It is possible that the presence of a small amount of an abnormal, truncated protein could act as a seed for a conformational change that would result in the conversion of PrPc to PrPsc (Prusiner 1991). This project sets out to investigate the differences between the cellular processing of the wild type GPI-anchored protein and a mutant protein where addition of the GPI has been prevented. The mutant is investigated to show that the engineered mutation does indeed give rise to a GPI-less form and the size, glycosylation status, immunoreactivity and cellular location of the two proteins are investigated firstly in a cell-free system and secondly in tissue culture cells. The question of whether PrPsc can be produced when the GPI-anchor is absent will be addressed by subsequent studies of these mutations in transgenic mice.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available