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Blastocyst Injection of Wild Type Embryonic Stem Cells Induces Global Corrections in Mdx Mice
Duchenne muscular dystrophy (DMD) is an incurable neuromuscular degenerative disease, caused by a mutation in the dystrophin gene. Mdx mice recapitulate DMD features. Here we show that injection of wild-type (WT) embryonic stem cells (ESCs) into mdx blastocysts produces mice with improved pathology...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653195/ https://www.ncbi.nlm.nih.gov/pubmed/19277212 http://dx.doi.org/10.1371/journal.pone.0004759 |
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author | Stillwell, Elizabeth Vitale, Joseph Zhao, Qingshi Beck, Amanda Schneider, Joel Khadim, Farah Elson, Genie Altaf, Aneela Yehia, Ghassan Dong, Jia-hui Liu, Jing Mark, Willie Bhaumik, Mantu Grange, Robert Fraidenraich, Diego |
author_facet | Stillwell, Elizabeth Vitale, Joseph Zhao, Qingshi Beck, Amanda Schneider, Joel Khadim, Farah Elson, Genie Altaf, Aneela Yehia, Ghassan Dong, Jia-hui Liu, Jing Mark, Willie Bhaumik, Mantu Grange, Robert Fraidenraich, Diego |
author_sort | Stillwell, Elizabeth |
collection | PubMed |
description | Duchenne muscular dystrophy (DMD) is an incurable neuromuscular degenerative disease, caused by a mutation in the dystrophin gene. Mdx mice recapitulate DMD features. Here we show that injection of wild-type (WT) embryonic stem cells (ESCs) into mdx blastocysts produces mice with improved pathology and function. A small fraction of WT ESCs incorporates into the mdx mouse nonuniformly to upregulate protein levels of dystrophin in the skeletal muscle. The chimeric muscle shows reduced regeneration and restores dystrobrevin, a dystrophin-related protein, in areas with high and with low dystrophin content. WT ESC injection increases the amount of fat in the chimeras to reach WT levels. ESC injection without dystrophin does not prevent the appearance of phenotypes in the skeletal muscle or in the fat. Thus, dystrophin supplied by the ESCs reverses disease in mdx mice globally in a dose-dependent manner. |
format | Text |
id | pubmed-2653195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26531952009-03-11 Blastocyst Injection of Wild Type Embryonic Stem Cells Induces Global Corrections in Mdx Mice Stillwell, Elizabeth Vitale, Joseph Zhao, Qingshi Beck, Amanda Schneider, Joel Khadim, Farah Elson, Genie Altaf, Aneela Yehia, Ghassan Dong, Jia-hui Liu, Jing Mark, Willie Bhaumik, Mantu Grange, Robert Fraidenraich, Diego PLoS One Research Article Duchenne muscular dystrophy (DMD) is an incurable neuromuscular degenerative disease, caused by a mutation in the dystrophin gene. Mdx mice recapitulate DMD features. Here we show that injection of wild-type (WT) embryonic stem cells (ESCs) into mdx blastocysts produces mice with improved pathology and function. A small fraction of WT ESCs incorporates into the mdx mouse nonuniformly to upregulate protein levels of dystrophin in the skeletal muscle. The chimeric muscle shows reduced regeneration and restores dystrobrevin, a dystrophin-related protein, in areas with high and with low dystrophin content. WT ESC injection increases the amount of fat in the chimeras to reach WT levels. ESC injection without dystrophin does not prevent the appearance of phenotypes in the skeletal muscle or in the fat. Thus, dystrophin supplied by the ESCs reverses disease in mdx mice globally in a dose-dependent manner. Public Library of Science 2009-03-11 /pmc/articles/PMC2653195/ /pubmed/19277212 http://dx.doi.org/10.1371/journal.pone.0004759 Text en Stillwell et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Stillwell, Elizabeth Vitale, Joseph Zhao, Qingshi Beck, Amanda Schneider, Joel Khadim, Farah Elson, Genie Altaf, Aneela Yehia, Ghassan Dong, Jia-hui Liu, Jing Mark, Willie Bhaumik, Mantu Grange, Robert Fraidenraich, Diego Blastocyst Injection of Wild Type Embryonic Stem Cells Induces Global Corrections in Mdx Mice |
title | Blastocyst Injection of Wild Type Embryonic Stem Cells Induces Global Corrections in Mdx Mice |
title_full | Blastocyst Injection of Wild Type Embryonic Stem Cells Induces Global Corrections in Mdx Mice |
title_fullStr | Blastocyst Injection of Wild Type Embryonic Stem Cells Induces Global Corrections in Mdx Mice |
title_full_unstemmed | Blastocyst Injection of Wild Type Embryonic Stem Cells Induces Global Corrections in Mdx Mice |
title_short | Blastocyst Injection of Wild Type Embryonic Stem Cells Induces Global Corrections in Mdx Mice |
title_sort | blastocyst injection of wild type embryonic stem cells induces global corrections in mdx mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653195/ https://www.ncbi.nlm.nih.gov/pubmed/19277212 http://dx.doi.org/10.1371/journal.pone.0004759 |
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