Analysis of Dystrophin Expression after Activation of Myogenesis in Amniocytes, Chorionic-Villus Cells, and Fibroblasts -- A New Method for Diagnosing Duchenne's Muscular Dystrophy

Sancho, Sara; Mongini, Tiziana; Tanji, Kurenai; Tapscott, S J; Walker, Wf; Weintraub, Harold; Miller, A. Dusty; Af, Miranda

doi:10.1056/nejm199309233291303

Cited by 40 publications

(12 citation statements)

References 17 publications

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“…Therefore, to analyze the chromatin structure in the region of the hypersensitive site in skeletal muscle cells, DM fibroblasts were infected with a retrovirus expressing the myogenic determination gene MyoD and the selectable marker neomycin phosphotransferase. Previous work has shown that the expression of MyoD can convert fibroblasts to skeletal muscle cells (13,15), and this approach was used because primary muscle cultures from affected individuals were not available. After selection in G418 the MyoD-expressing cells demonstrated conversion to a skeletal muscle phenotype (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure.

Otten

Tapscott²

1995

Proc. Natl. Acad. Sci. U.S.A.

172

107

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Myotonic dystrophy is caused by an expansion of a CTG triplet repeat sequence in the 3' noncoding region of a protein kinase gene, yet the mechanism by which the triplet repeat expansion causes disease remains unknown. This report demonstrates that a DNase I hypersensitive site is positioned 3' of the triplet repeat in the wild-type allele in both fibroblasts and skeletal muscle cells. In three unrelated individuals with myotonic dystrophy that have large expansions of the triplet repeat, the allele with the triplet repeat expansion exhibited both overall DNase I resistance and inaccessibility of nucleases to the adjacent hypersensitive site. These results indicate that the triplet repeat expansion alters the adjacent chromatin structure, establishing a region of condensed chromatin, and suggests a molecular mechanism for myotonic dystrophy.

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Section: Resultsmentioning

confidence: 99%

Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure.

Otten

Tapscott²

1995

Proc. Natl. Acad. Sci. U.S.A.

172

107

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“…Since myoblasts from patient P1 were not available, fibroblasts from controls and patients P1 and P2 were converted into myoblasts by retroviral transfection of the muscle differentiation gene, MyoD, as described earlier [15]. These myoblasts were maintained in culture in the same growth medium as described above.…”

Section: Cell Culturementioning

confidence: 99%

Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations

Salviati

Hernandez-Rosa

Walker

et al. 2002

Biochemical Journal

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Human SCO2 is a nuclear-encoded Cu-binding protein, presumed to be responsible for the insertion of Cu into the mitochondrial cytochrome c oxidase (COX) holoenzyme. Mutations in SCO2 are associated with cardioencephalomyopathy and COX deficiency. Studies in yeast and bacteria have shown that Cu supplementation can restore COX activity in cells harbouring mutations in genes involving Cu transport. Therefore we investigated whether Cu supplementation could restore COX activity in cultured cells from patients with SCO2 mutations. Our data demonstrate that the COX deficiency observed in fibroblasts, myoblasts and myotubes from patients with SCO2 mutations can be restored to almost normal levels by the addition of CuCl2 to the growth medium.

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“…MyoD, rather than a neuronal bHLH protein, was used for this analysis since the target genes for MyoD have been identified. In contrast to many nontransformed cell types, where MyoD expression is sufficient to activate skeletal myogenesis (12,50), forced expression of MyoD failed to convert a majority of tested neural tumor lines to muscle. In all cases, myogenesis was restored in heterokaryons between the tumor cells and fibroblasts, indicating that the inactivity of MyoD in the tumor cells reflected the deficiency of a factor necessary for myogenesis and allowing us to establish complementation groups among different tumors on the basis of the ability to execute a myogenic differentiation program.…”

mentioning

confidence: 63%

“…Since previous work has demonstrated that MyoD can convert many primary cells and cell lines to muscle (12,50), the inactivity of MyoD in the tumor cell lines is unusual and indicates that during tumor progression there may be a selection for alterations that prevent bHLH activity. Alternatively, the tumors may have arisen from a lineage position where the activity of MyoD, and perhaps other bHLH proteins, is precluded.…”

Section: Discussionmentioning

confidence: 99%

Tumor Cell Complementation Groups Based on Myogenic Potential: Evidence for Inactivation of Loci Required for Basic Helix-Loop-Helix Protein Activity

Gerber

Tapscott

1996

Molecular and Cellular Biology

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Basic helix-loop-helix (bHLH) proteins mediate terminal differentiation in many lineages. By using the bHLH protein MyoD, which can dominantly activate the myogenic differentiation program in numerous cell types, we demonstrated that recessive defects in bHLH protein function are present in human tumor lines. In contrast to prior work with primary cell cultures, MyoD did not activate the myogenic program in six of the eight tumor lines we tested. Cell fusions between the MyoD-defective lines and fibroblasts restored MyoD activity, indicating that the deficiency of a gene or factor prevents bHLH protein function in the tumor lines. Fusions between certain pairings of the MyoD-defective lines also restored MyoD activity, allowing the tumor lines to be assigned to complementation groups on the basis of their ability to execute the myogenic program and indicating that multiple mechanisms exist for abrogation of bHLH protein activity. These groups provide a basis for identifying genes critical for bHLH-mediated differentiation and tumor progression by using genetic complementation.

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Analysis of Dystrophin Expression after Activation of Myogenesis in Amniocytes, Chorionic-Villus Cells, and Fibroblasts -- A New Method for Diagnosing Duchenne's Muscular Dystrophy

Abstract: Immunocytochemical analysis of dystrophin in genetically altered non-muscle cells is feasible and may be applicable to the prenatal and postnatal diagnosis of Duchenne's muscular dystrophy when conventional DNA analysis is not informative.

Cited by 40 publications

References 17 publications

Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure.

Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure.

Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations

Tumor Cell Complementation Groups Based on Myogenic Potential: Evidence for Inactivation of Loci Required for Basic Helix-Loop-Helix Protein Activity

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