Myogenic Conversion of Human Non-Muscle Cells for the Diagnosis and Therapy of Neuromuscular Diseases
Control of tissue-specific gene expression in eukaryotes represents one of the central unanswered questions in developmental biology. Davis et al (1) isolated a muscle regulatory cDNA called MyoD from mouse cells: when transfected into fibroblasts or adipocytes, MyoD converts these cells to myoblasts, which, under appropriate conditions, can fuse and differentiate. Later, several additional genes, myd (2), myogenin (3) and Myf-5 (4), also capable of stably converting non-muscle cells to myoblasts were isolated. The availability of these probes will lead to a better understanding of the ordered regulation of gene expression in muscle and other differentiating tissues. These factors that can produce myogenic conversion may also have practical applications in the diagnosis or even the treatment of hereditary human myopathies, such as Duchenne Muscular dystrophy (DMD). This will be the theme of this presentation.
KeywordsDUCHENNE Muscular Dystrophy Duchenne Muscular Dystrophy DUCHENNE Muscular Dystrophy Patient Anterior Tibial Muscle Human Myoblast
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- 4.T. Braun, G. Buschhausen-Denker, E. Bober, E. Tannich and H. H. Arnold, A novel human muscle factor related to but distinct from MyoDl induces myogenic conversion in 10Th fibroblasts, EMBO J. 8: 701 (1989).Google Scholar
- 5.B. T. Darras, P. Blattner, J. F. Harper, A. J. Spiro, S. Alter, and U. Francke, Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA: location of breakpoints on Hindlll and BglII exon-containing fragment maps, meiotic and mitotic origin of the mutations, Am. J. Hum. Genet. 43: 620 (1988).PubMedGoogle Scholar
- 8.S. M. Forrest, G. S. Cross, A. Speer, D. Gardner-Medwin, J. Burn, and K.E. Davies, Preferential deletion of exons in Duchenne and Becker muscular dystrophies, Nature 329: 638 (1987).Google Scholar
- 11.H. Sugita, K. Arahata, T. Ishiguro, Y. Suhara, T. Tsukahara, S. Ishiura, C. Eguchi, I. Nonaka, and E. Ozawa, Negative immunostaining of Duchenne muscular dystrophy and mdx muscle surface membrane with antibody against synthetic peptide fragment predicted from DMD cDNA, Proc. Jap. Acad. (B) 64: 210 (1988).Google Scholar
- 12.E. E. Zubrzycka-Gaarn, D. E. Bulman, G. Karpati, A. H. M. Burghes, B. Belfall, H. J. Klamut, J. Talbot, R. S. Hodges, P. N. Ray, and R. G. Worton, The Duchenne muscular dystrophy gene product is localized in the sarcolemma of human skeletal muscle, Nature 333: 466 (1988).PubMedCrossRefGoogle Scholar
- 13.M. S. Ecob-Prince, M. A. Hill, and A. E. Brown, Localization of dystrophin in cultures of human muscles, Muscle and Nerve 12: 594 (1989).Google Scholar
- 19.H. Weintraub, S. J. Tapscott, R. L. Davis, M. J. Thayer,M. A. Adam, A. B. Lassar, and A. D. M.ller, Activation of muscle-specific genes in pigment, nerve, fat, liver and fibroblast cell lines by forced expression of MyoD, Proc. Natl. Acad. Sci. USA. 86: 5434 (1989).Google Scholar
- 20.T. Mongini, A. F. Miranda, E. Bonilla, A. D. Miller, W. E. Wright, and H. Weintraub, Manuscript in preparation.Google Scholar
- 21.Hurko, E. P. Hoffman, L. McKee, D. R. Johns, and L. M. Kunkel, Dystrophin analysis in clonal myoblasts derived from a Duchenne muscular dystrophy carrier, Am. J. Hum. Genet. 44: 820 (1989).Google Scholar
- 26.A. F. Miranda and T. Mongini, Diseased muscle in tissue culture, in: “Myology”, A. G. Engel and B. Q. Banker, eds., McGraw Hill Book Comp., New York (1986).Google Scholar