biostudies-literatureLancioni ATelethonHoward Hughes Medical InstituteNCRR NIH HHSNHLBI NIH HHSNINDS NIH HHSNIAMS NIH HHS4644-54https://www.ebi.ac.uk/biostudies/studies/S-EPMC3209833biostudies-literatureUnknown20(23)Cardiomyopathy is a puzzling complication in addition to skeletal muscle pathology for patients with mutations in β-, γ- or δ-sarcoglycan (SG) genes. Patients with mutations in α-SG rarely have associated cardiomyopathy, or their cardiac pathology is very mild. We hypothesize that a fifth SG, ε-SG, may compensate for α-SG deficiency in the heart. To investigate the function of ε-SG in striated muscle, we generated an Sgce-null mouse and a Sgca-;Sgce-null mouse, which lacks both α- and ε-SGs. While Sgce-null mice showed a wild-type phenotype, with no signs of muscular dystrophy or heart disease, the Sgca-;Sgce-null mouse developed a progressive muscular dystrophy and a more anticipated and severe cardiomyopathy. It shows a complete loss of residual SGs and a strong reduction in both dystrophin and dystroglycan. Our data indicate that ε-SG is important in preventing cardiomyopathy in α-SG deficiency.Human molecular geneticsCombined deficiency of alpha and epsilon sarcoglycan disrupts the cardiac dystrophin complex.PMC3209833F32AR48742R01AR051199-ST32HL07121UL1RR0024979TGM11Z06U54NS053672-S1U54NS053672R01AR051199Cacciottolo MNigro GCampbell KPRotundo ILD'Orsi LAurino SAcampora DKobayashi YMPiluso GNigro VLancioni AfalseCombined deficiency of alpha and epsilon sarcoglycan disrupts the cardiac dystrophin complex.Cardiomyopathy is a puzzling complication in addition to skeletal muscle pathology for patients with mutations in β-, γ- or δ-sarcoglycan (SG) genes. Patients with mutations in α-SG rarely have associated cardiomyopathy, or their cardiac pathology is very mild. We hypothesize that a fifth SG, ε-SG, may compensate for α-SG deficiency in the heart. To investigate the function of ε-SG in striated muscle, we generated an Sgce-null mouse and a Sgca-;Sgce-null mouse, which lacks both α- and ε-SGs. While Sgce-null mice showed a wild-type phenotype, with no signs of muscular dystrophy or heart disease, the Sgca-;Sgce-null mouse developed a progressive muscular dystrophy and a more anticipated and severe cardiomyopathy. It shows a complete loss of residual SGs and a strong reduction in both dystrophin and dystroglycan. Our data indicate that ε-SG is important in preventing cardiomyopathy in α-SG deficiency.2011-01-01T00:00:00Z2011 Dec2025-07-02T03:04:55.709Z2025-07-02T03:04:55.709ZS-EPMC32098332189049410.1093/hmg/ddr398