title: Normal innervation and differentiation of X-linked myotubular myopathy muscle cells in a nerve-muscle coculture system.
abstract: To study the pathogenesis of X-linked recessive myotubular myopathy (XLMTM), we used a nerve-muscle coculture system which allows the reconstitution of functional motor units in vitro after coupling of human skeletal muscle cells with embryonic rat spinal cord explants. We used three skeletal muscle cell lines derived from subjects with known mutations in the MTM1 gene (two from embryonic tissues, associated with mutations predicted to give a severe phenotype, and one from a neonate still alive at 3 years 6 months and exhibiting a mild phenotype). We compared these three XLMTM muscle cell cultures with control cultures giving special attention to behaviour of living cocultures (formation of the myofibres, contractile activity, survival), expression of muscular markers (desmin, dystrophin, alpha-actinin, troponin-T, myosin heavy chain isoforms), and nerve-muscle interactions (expression and aggregation of the nicotinic acetylcholine receptors). We were unable to reproduce any 'myotubular' phenotype since XLMTM muscle cells behaved like normal cells with regard to all the investigated parameters. Our results suggest that XLMTM muscle might be intrinsically normal and emphasize the possible involvement of the myotubularin-deficient motor neurons in the development of the disease.
authors.affiliation: Laboratoire de Pathologie des Communications entre Cellules Nerveuses et Musculaires (UPRES 2308), UFR des Sciences Pharmaceutiques, BP 24, 74 route du Rhin, 67401 Illkirch Cedex, France.
authors.forename: O M
authors.initials: OM
authors.lastname: Dorchies
authors.forename: J
authors.initials: J
authors.lastname: Laporte
authors.forename: S
authors.initials: S
authors.lastname: Wagner
authors.forename: C
authors.initials: C
authors.lastname: Hindelang
authors.forename: J M
authors.initials: JM
authors.lastname: Warter
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
authors.forename: P
authors.initials: P
authors.lastname: Poindron
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000196:embryology / Q000294:innervation* / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D009210:Myofibrils / Q000378:metabolism / Q000648:ultrastructure; D020914:Myopathies, Structural, Congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009417:Nerve Tissue / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D014960:X Chromosome / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; D011978:Receptors, Nicotinic; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin