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Title: Defects in the nuclear proteins, emerin and lamins, lead to Emery-Dreifuss muscular dystrophy
Author: Fairley, E. A. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2001
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The aim of my study was to determine how the inner nuclear protein emerin and nuclear A-type lamins cause X-linked and autosomal dominant Emery-Dreifuss muscular dystrophy. Initial experiments demonstrated that the expression and localisation of endogenous emerin, A and B-type lamins in primary and tissue-cultured cells were cell type specific. The majority of emerin mutations, identified in patients, produce no detectable protein although there are a few cases that produce modified forms. To test whether these modified forms of emerin are mis-targeted, EGFP-constructs that mimic these mutations were transfected into undifferentiated C2C12 myoblasts. Both wild type and all the mutant emerins were targeted to the nuclear membrane, but the mutants to a lesser extent. Complete removal of the transmembrane region and carboxyl terminal tail relocated emerin to the nucleoplasm. These results indicate that the carboxyl terminal domain of emerin contains the major targeting determinants and the amino terminal domain effects its ability to be retained at the nuclear membrane by affecting its interactions with nuclear components. To study the localisation of mutant forms of A-type lamins, expressed in autosomal dominant forms of EDMD patients, EGFP-lamin A constructs reflecting these mutations were transfected into COS-7 fibroblasts and C2C12 myoblasts. The data obtained suggests that the carboxyl terminal domain is involved in lamin A assembly and targeting.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available