title: Restoration of normal function in genetically defective myotubes by spontaneous fusion with fibroblasts.
abstract: Muscular dysgenesis in mice is a genetic disease of skeletal muscle caused by the recessive mutation mdg. Muscle fibres in affected mice are paralysed because of the failure of excitation-contraction coupling. Unlike normal myotubes in primary culture, dysgenic myotubes do not contract, either spontaneously or in response to electrical stimulation. The deficiency results from mutation of the gene for the skeletal muscle dihydropyridine receptor, an essential sarcolemmal component both of excitation-contraction coupling and of the slow calcium-ion channel. It has recently been shown that the addition of fibroblasts from normal (but not dysgenic) mice to cultures of dysgenic myotubes can restore spontaneous contractions in a small fraction of these myotubes, but the mechanism for this 'rescue' was not determined. In principle, if fibroblast nuclei were able to incorporate into myotubes, such nuclei could then supply the missing muscle-specific gene product. We have now investigated this possibility using nuclear, cytoplasmic and plasmalemmal markers. We report that the rescue to contractile ability in genetically paralysed dysgenic muscle is mediated by the previously unrecognized ability of fibroblasts to fuse spontaneously with developing myotubes.
authors.affiliation: Department of Physiology, Colorado State University, Fort Collins 80523.
authors.forename: N
authors.initials: N
authors.lastname: Chaudhari
authors.forename: R
authors.initials: R
authors.lastname: Delay
authors.forename: K G
authors.initials: KG
authors.lastname: Beam
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005819:Genetic Markers / Q000032:analysis; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000502:physiology / Q000503:physiopathology; D009135:Muscular Diseases / Q000235:genetics* / Q000503:physiopathology; D051381:Rats; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D005819:Genetic Markers; D001616:beta-Galactosidase