title: Desmin immunolocalisation in autosomal dominant Emery-Dreifuss muscular dystrophy.
abstract: Autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD) is one of a number of allelic disorders caused by mutations in the nuclear lamina proteins, lamins A and C. The disorder is characterised by the early onset of skeletal muscle weakness and joint contractures and later, by dilated cardiomyopathy and cardiac arrythmias. Although the pathophysiology is not understood, one theory suggests that disordered structural organisation at weakened nuclei in contractile cells may underlie the disease. Previous work shows that mice deficient in lamin A/C develop similar skeletal and cardiac muscle signs to patients with AD-EDMD and ultrastructural examination of muscle from these mice shows abnormal localisation of desmin. We hypothesised therefore that desmin localisation may be abnormal in muscle or cells from patients with AD-EDMD and/or in cells expressing mutant lamins. In order to evaluate this, desmin immunolocalisation was determined in skeletal muscle biopsy sections from patients with AD-EDMD and cell lines including MyoD-transfected fibroblast-derived myotubes from AD-EDMD patients and murine embryonic stem cell-derived cardiomyocytes stably transfected with mutant human lamin A. Ultrastructural examination of patient muscle was also performed. Desmin was expressed and localised normally in patient muscle and cell lines and ultrastructural examination was similar to controls. These results fail to provide any evidence that dominant mutations in lamin A/C lead to a disorganisation of the desmin associated cytoskeleton.
authors.affiliation: Dubowitz Neuromuscular Unit, Department of Paediatrics, Hammersmith Hospital, Imperial College, London, United Kingdom. rpiercy@rvc.ac.uk
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Piercy
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhou
authors.forename: Lucy
authors.initials: L
authors.lastname: Feng
authors.forename: Ana
authors.initials: A
authors.lastname: Pombo
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Susan C
authors.initials: SC
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003893:Desmin / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000502:physiology; D017570:MyoD Protein / Q000494:pharmacology; D014162:Transfection / Q000379:methods
chemical_list: D003893:Desmin; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D049452:Green Fluorescent Proteins