Blastocyst injection of wild type embryonic stem cells induces global corrections in Mdx mice Journal Article
| Authors: | Stillwell, E.; Vitale, J.; Zhao, Q.; Beck, A.; Schneider, J.; Khadim, F.; Elson, G.; Altaf, A.; Yehia, G.; Dong, J. H.; Liu, J.; Mark, W.; Bhaumik, M.; Grange, R.; Fraidenraich, D. |
| Article Title: | Blastocyst injection of wild type embryonic stem cells induces global corrections in Mdx mice |
| Abstract: | 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. © 2009 Stillwell et al. |
| Keywords: | controlled study; genetics; histopathology; nonhuman; pathophysiology; methodology; protein localization; animal cell; mouse; animal; animals; mice; animal tissue; mus; embryo; embryonic stem cell; animal experiment; animal model; stem cell transplantation; pathology; transplantation; wild type; mice, inbred c57bl; physiology; c57bl mouse; chimera; regeneration; prenatal development; chemistry; gene therapy; embryonic stem cells; upregulation; concentration response; skeletal muscle; microinjections; blastocyst; embryo transfer; fat; dystrobrevin; dystrophin; apo dystrophin 1; apo-dystrophin 1; dystrophin associated protein; duchenne muscular dystrophy; lipid analysis; muscle function; muscle regeneration; x chromosome linked muscular dystrophic mouse; animal muscular dystrophy; lactose operon; microinjection; dystrophin-associated proteins; lac operon; mice, inbred mdx; muscle, skeletal; muscular dystrophy, animal; muscular dystrophy, duchenne |
| Journal Title: | PLoS ONE |
| Volume: | 4 |
| Issue: | 3 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2009-03-11 |
| Start Page: | e4759 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0004759 |
| PUBMED: | 19277212 |
| PROVIDER: | scopus |
| PMCID: | PMC2653195 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "Art. No.: e4759" - "Source: Scopus" |
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