© 1992 Oxford University Press
RESEARCH-ARTICLE |
Human dystrophin expression corrects the myopathic phenotype in transgenic mdx mice
Unit of Veterinary Molecular and Cellular Biology, Department of Veterinary Basic Sciences, The Royal Veterinary College London NW1 OTU 1Department of Experimental Pathology, UMDS, Guy's Hospital, London Bridge London SE1 9RT 2Molecular Genetics Group, Institute of Molecular Medicine, John Radcliffe Hospital Headington, Oxford OX3 9DU, UK
*To whom correspondence should be addressed
Received November 19, 1991; Revised January 28, 1992; Accepted January 28, 1992
Duchenne and the less severe Becker form of muscular dystrophy (DMD, BMD) result from genetic deficiency in the level and/or activity of the protein dystrophin. The recent availability of cDNA based minigenes encoding recombinant dystrophin polypeptides has raised the possibility of somatic gene transfer as a therapeutic approach to treat dystrophin deficiency. In this respect, the mdx mouse provides a useful model of DMD exhibiting features characteristic of both the early myopathic and later fibrotic phases of the human disease. Using a mutated human cDNA, compatible in size with virus-based somatic gene transfer vectors, the pathophysiological consequences of restoring dystrophin expression have been examined in transgenic mdx mice. Transgene expression was correlated with a marked reduction of the skeletal myofibre necrosis and regeneration which is a major feature of the dystrophin-deficient phenotype in young mdx mice. The cDNA construct which is based on a very mild BMD phenotype thus encodes a highly functional dystrophin molecule whose reduced size renders it an attractive candidate for development as a therapeutic gene transfer reagent.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Yin, H. M. Moulton, C. Betts, Y. Seow, J. Boutilier, P. L. Iverson, and M. J.A. Wood A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice Hum. Mol. Genet., November 15, 2009; 18(22): 4405 - 4414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yin, H. M. Moulton, Y. Seow, C. Boyd, J. Boutilier, P. Iverson, and M. J.A. Wood Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function Hum. Mol. Genet., December 15, 2008; 17(24): 3909 - 3918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Li, Y. Yue, and D. Duan Preservation of Muscle Force in Mdx3cv Mice Correlates with Low-Level Expression of a Near Full-Length Dystrophin Protein Am. J. Pathol., May 1, 2008; 172(5): 1332 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Burkin, G. Q. Wallace, D. J. Milner, E. J. Chaney, J. A. Mulligan, and S. J. Kaufman Transgenic Expression of {alpha}7{beta}1 Integrin Maintains Muscle Integrity, Increases Regenerative Capacity, Promotes Hypertrophy, and Reduces Cardiomyopathy in Dystrophic Mice Am. J. Pathol., January 1, 2005; 166(1): 253 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. ENGVALL and U. M. WEWER The new frontier in muscular dystrophy research: booster genes FASEB J, September 1, 2003; 17(12): 1579 - 1584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Fabb, D. J. Wells, P. Serpente, and G. Dickson Adeno-associated virus vector gene transfer and sarcolemmal expression of a 144 kDa micro-dystrophin effectively restores the dystrophin-associated protein complex and inhibits myofibre degeneration in nude/mdx mice Hum. Mol. Genet., April 1, 2002; 11(7): 733 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. Maria, C. D. Medina, K. B.N. Hoang, and M. Ian Phillips Topical Review: Gene Therapy for Neurologic Disease: Benchtop Discoveries to Bedside Applications. 2. The Bedside J Child Neurol, February 1, 1997; 12(2): 77 - 84. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Dunckley, K. Wells, T. Piper, D. Wells, and G Dickson Independent localization of dystrophin N- and C-terminal regions to the sarcolemma of mdx mouse myofibres in vivo J. Cell Sci., January 6, 1994; 107(6): 1469 - 1475. [Abstract] [PDF]
|
|
|
|
 |
|
 M. A. Morsy, K. Mitani, P. Clemens, and C. T. Caskey Progress Toward Human Gene Therapy JAMA, November 17, 1993; 270(19): 2338 - 2345. [Abstract] [PDF]
|
|
|
|
|
|
G. Dickson, A. Azad, G. E. Morris, H. Simon, M. Noursadeghi, and F. S. Walsh Co-localization and molecular association of dystrophin with laminin at the surface of mouse and human myotubes J. Cell Sci., December 1, 1992; 103(4): 1223 - 1233. [Abstract] [PDF]
|
|