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Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules
BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most common muscle dystrophy in adults. The disease is caused by a triplet expansion in the 3'end of the myotonic dystrophy protein kinase (DMPK) gene. In order to develop a human cell model for investigation of possible effects of antisense an...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226528/ https://www.ncbi.nlm.nih.gov/pubmed/22078098 http://dx.doi.org/10.1186/1756-0500-4-490 |
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author | Larsen, Jan Pettersson, Olof J Jakobsen, Maria Thomsen, Rune Pedersen, Christina B Hertz, Jens M Gregersen, Niels Corydon, Thomas J Jensen, Thomas G |
author_facet | Larsen, Jan Pettersson, Olof J Jakobsen, Maria Thomsen, Rune Pedersen, Christina B Hertz, Jens M Gregersen, Niels Corydon, Thomas J Jensen, Thomas G |
author_sort | Larsen, Jan |
collection | PubMed |
description | BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most common muscle dystrophy in adults. The disease is caused by a triplet expansion in the 3'end of the myotonic dystrophy protein kinase (DMPK) gene. In order to develop a human cell model for investigation of possible effects of antisense and RNAi effector molecules we have used lentiviral mediated myoD-forced myogenesis of DM1 patient fibroblasts. FINDINGS: Transduced fibroblasts show a multinuclear phenotype and express the differentiation marker myogenin. Furthermore, fluorescence in situ hybridization (FISH) analysis revealed a statistical significant increase in the amount of nuclear foci in DM1 patient fibroblasts after myogenesis. Finally, no nuclear foci were found after treatment with oligonucleotides targeting the repeat expansions. CONCLUSIONS: The abundance of nuclear foci in DM1 patient fibroblasts increase following myogenesis, as visualized by FISH analysis. Foci were eradicated after treatment with antisense oligonucleotides. Thus, we propose that the current cell model is suitable for testing of novel treatment modalities. |
format | Online Article Text |
id | pubmed-3226528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32265282011-11-30 Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules Larsen, Jan Pettersson, Olof J Jakobsen, Maria Thomsen, Rune Pedersen, Christina B Hertz, Jens M Gregersen, Niels Corydon, Thomas J Jensen, Thomas G BMC Res Notes Short Report BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most common muscle dystrophy in adults. The disease is caused by a triplet expansion in the 3'end of the myotonic dystrophy protein kinase (DMPK) gene. In order to develop a human cell model for investigation of possible effects of antisense and RNAi effector molecules we have used lentiviral mediated myoD-forced myogenesis of DM1 patient fibroblasts. FINDINGS: Transduced fibroblasts show a multinuclear phenotype and express the differentiation marker myogenin. Furthermore, fluorescence in situ hybridization (FISH) analysis revealed a statistical significant increase in the amount of nuclear foci in DM1 patient fibroblasts after myogenesis. Finally, no nuclear foci were found after treatment with oligonucleotides targeting the repeat expansions. CONCLUSIONS: The abundance of nuclear foci in DM1 patient fibroblasts increase following myogenesis, as visualized by FISH analysis. Foci were eradicated after treatment with antisense oligonucleotides. Thus, we propose that the current cell model is suitable for testing of novel treatment modalities. BioMed Central 2011-11-11 /pmc/articles/PMC3226528/ /pubmed/22078098 http://dx.doi.org/10.1186/1756-0500-4-490 Text en Copyright ©2011 Jensen et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Short Report Larsen, Jan Pettersson, Olof J Jakobsen, Maria Thomsen, Rune Pedersen, Christina B Hertz, Jens M Gregersen, Niels Corydon, Thomas J Jensen, Thomas G Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules |
title | Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules |
title_full | Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules |
title_fullStr | Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules |
title_full_unstemmed | Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules |
title_short | Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules |
title_sort | myoblasts generated by lentiviral mediated myod transduction of myotonic dystrophy type 1 (dm1) fibroblasts can be used for assays of therapeutic molecules |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226528/ https://www.ncbi.nlm.nih.gov/pubmed/22078098 http://dx.doi.org/10.1186/1756-0500-4-490 |
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