{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vitale JM"],"funding":["NHLBI NIH HHS"],"pagination":["1807-13"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3346830"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["125(Pt 7)"],"pubmed_abstract":["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."],"journal":["Journal of cell science"],"pubmed_title":["Dystrophin-compromised sarcoglycan-δ-knockout diaphragm requires full wild-type embryonic stem cell reconstitution for correction."],"pmcid":["PMC3346830"],"funding_grant_id":["R01 HL106511","R21 HL094905","T32 HL069752","R21-HL094905","T31-HL069752","T32 HL069752-09"],"pubmed_authors":["Bhaumik M","Fraidenraich D","Schneider JS","Beck AJ","Zhao Q","Gordan R","Vitale JM","Chang C","Michaels J"],"additional_accession":[]},"is_claimable":false,"name":"Dystrophin-compromised sarcoglycan-δ-knockout diaphragm requires full wild-type embryonic stem cell reconstitution for correction.","description":"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.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Apr","modification":"2025-04-18T20:45:10.399Z","creation":"2019-03-27T00:53:13Z"},"accession":"S-EPMC3346830","cross_references":{"pubmed":["22328522"],"doi":["10.1242/jcs.100537"]}}