Investigation of NET localization in muscular disease
Research type
Research Study
Full title
Investigation of nuclear envelope transmembrane protein (NET) localization in muscular disease compared to controls and functional investigations to determine the role of NETs in muscular diseases.
IRAS ID
177946
Contact name
Eric Schirmer
Contact email
Sponsor organisation
The University of Edinburgh
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
The nuclear envelope (NE) is a protective barrier that separates the genetic material (genes) in the nucleus from the rest of the cell. Many proteins in the NE contribute to the regulation of gene expression that distinguishes different cell types e.g. why a liver cell has its particular properties and why a muscle cell has its particular properties. Several proteins in the NE, when mutated, cause two different muscular dystrophies, Emery-Dreifuss muscular dystrophy (EDMD) that affects more tendons in calves and upper arms and Limb girdle muscular dystrophy (LGMD) that affects more upper leg and hip muscles. Different NE proteins can cause different variants of the same disease and some NE proteins can cause multiple distinct diseases. For example, lamin A is responsible for variants of EDMD, LGMD and cardiomyopathy with conduction defect. To explain how the same protein can affect distinct muscle groups in different diseases it has been suggested that other proteins more specific to these muscle groups mediate the lamin-directed pathology. The mutated genes that cause EDMD have only been identified in about half of the clinical cases of EDMD. We have recently found mutations in several novel muscle-specific NE proteins in these EDMD patients for which the causative gene was not known. We predict that these may be the hypothesized mediators of lamin-directed pathology and that they might cause and/or mediate pathology in other muscular dystrophies for which the pattern of muscle groups in which they are
expressed matches the muscle groups damaged in the disease. Therefore, we propose to stain muscle biopsies from healthy controls and from patient muscle biopsies from a number of muscular dystrophy patients to determine 1) which specific muscle groups have these proteins at the NE, 2) if their expression or distribution is altered in muscular dystrophy patients.REC name
West of Scotland REC 5
REC reference
15/WS/0069
Date of REC Opinion
10 Apr 2015
REC opinion
Further Information Favourable Opinion