Dystrophin-compromised sarcoglycan-δ-knockout diaphragm requires full wild-type embryonic stem cell reconstitution for correction

Joseph M. Vitale, Joel S. Schneider, Amanda J. Beck, Qingshi Zhao, Corey Chang, Richard Gordan, Jennifer Michaels, Mantu Bhaumik, Diego Fraidenraich

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Limb-girdle muscular dystrophy-2F (LGMD-2F) is an incurable degenerative muscle disorder caused by a mutation in the sarcoglycan-δ (SGδ)-encoding gene (SGCD in humans). The lack of SGδ 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 SGδ-knockout (KO) blastocysts. ESC-derived SGδ 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 SGδ-KO skeletal muscle or heart. The inefficient process of ESC rescue was more evident in the SGδ-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 SGδ-KO mouse model of LGMD is not amenable to ESC treatment.

Original languageEnglish (US)
Pages (from-to)1807-1813
Number of pages7
JournalJournal of cell science
Issue number7
StatePublished - 2012

All Science Journal Classification (ASJC) codes

  • Cell Biology


  • Blastocyst
  • Chimera
  • Embryonic stem cells
  • Muscle
  • Sarcoglycanopathy


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