کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3081371 | 1189373 | 2007 | 9 صفحه PDF | دانلود رایگان |
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.
Journal: Neuromuscular Disorders - Volume 17, Issue 4, April 2007, Pages 276–284