| First Author | Vitale JM | Year | 2012 |
| Journal | J Cell Sci | Volume | 125 |
| Issue | Pt 7 | Pages | 1807-13 |
| PubMed ID | 22328522 | Mgi Jnum | J:197294 |
| Mgi Id | MGI:5492016 | Doi | 10.1242/jcs.100537 |
| Citation | Vitale JM, et al. (2012) Dystrophin-compromised sarcoglycan-delta-knockout diaphragm requires full wild-type embryonic stem cell reconstitution for correction. J Cell Sci 125(Pt 7):1807-13 |
| abstractText | Limb-girdle muscular dystrophy-2F (LGMD-2F) is an incurable degenerative muscle disorder caused by a mutation in the sarcoglycan-delta (SGdelta)-encoding gene (SGCD in humans). The lack of SGdelta results in the complete disruption of the sarcoglycan complex (SGC) in the skeletal and cardiac muscle within the larger dystrophin-glycoprotein complex (DGC). The long-term consequences of SG ablation on other members of the DGC are currently unknown. We produced mosaic mice through the injection of wild-type (WT) embryonic stem cells (ESCs) into SGdelta-knockout (KO) blastocysts. ESC-derived SGdelta was supplied to the sarcolemma of 18-month-old chimeric muscle, which resulted in the restoration of the SGC. Despite SGC rescue, and contrary to previous observations obtained with WT/mdx chimeras (a mouse rescue paradigm for Duchenne muscular dystrophy), low levels of ESC incorporation were insufficient to produce histological corrections in SGdelta-KO skeletal muscle or heart. The inefficient process of ESC rescue was more evident in the SGdelta-KO diaphragm, which had reduced levels of dystrophin and no compensatory utrophin, and needed almost full WT ESC reconstitution for histological improvement. The results suggest that the SGdelta-KO mouse model of LGMD is not amenable to ESC treatment. |
