Dystrophinopathy carrier determination and detection of protein deficiencies in muscular dystrophy using lentiviral MyoD-forced myogenesis

Cooper, Sandra T., Kizana, Eddy, Yates, Jonathon D., Lo, Harriet P., Yang, Nan, Wu, Zhan H., Alexander, Ian E. and North, Kathryn N. (2007) Dystrophinopathy carrier determination and detection of protein deficiencies in muscular dystrophy using lentiviral MyoD-forced myogenesis. Neuromuscular disorders, 17 4: 276-284. doi:10.1016/j.nmd.2006.12.010


Author Cooper, Sandra T.
Kizana, Eddy
Yates, Jonathon D.
Lo, Harriet P.
Yang, Nan
Wu, Zhan H.
Alexander, Ian E.
North, Kathryn N.
Title Dystrophinopathy carrier determination and detection of protein deficiencies in muscular dystrophy using lentiviral MyoD-forced myogenesis
Journal name Neuromuscular disorders   Check publisher's open access policy
ISSN 0960-8966
Publication date 2007-04
Sub-type Article (original research)
DOI 10.1016/j.nmd.2006.12.010
Volume 17
Issue 4
Start page 276
End page 284
Total pages 9
Place of publication Oxford ; New York
Publisher Pergamon Press
Language eng
Subject 060410 Neurogenetics
Abstract The objective of this study is to expand the applications of MyoD-forced myogenesis for research and diagnosis of human muscle disorders using a lentiviral vector (LVhMyoD) for efficient trans-differentiation of patient primary cells. LVhMyoD transduced cells readily formed striated, multinucleate myotubes expressing a wide range of genes associated with muscular dystrophy (dystrophin, dysferlin, sarcoglycans, caveolin-3) and congenital myopathy (nebulin, actin, desmin, tropomyosin, troponin). We demonstrate that MyoD gene-modified fibroblasts reproduce protein deficiencies associated with different forms of muscular dystrophy, and confirm that LVhMyoD gene-modified chorionic villus can be used successfully to determine the dystrophin status of the developing fetus, augmenting prenatal diagnosis of dystrophinopathy patients. Using muscle-specific cDNA derived from LVhMyoD gene-modified patient cells, we identified a female carrier bearing a large dystrophin deletion and a previously unidentified non-coding splice-site mutation within dystrophin in a Becker muscular dystrophy patient. This study highlights the significant potential of lentiviral MyoD-forced myogenesis for study of a wide range of human muscle disorders; a field constrained by the limited availability of human tissue. LVhMyoD gene-modified patient cells provide a renewable source of mutant protein and muscle-specific mRNA, facilitating accelerated mutation screening of large genes, molecular analyses of splicing abnormalities and study of disease-causing mutations
Keyword MyoD-forced myogenesis
Muscular dystrophy
Myopathy
Diagnosis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 12 Feb 2009, 11:09:05 EST by Mary-Anne Marrington on behalf of Institute for Molecular Bioscience