Combined deficiency of alpha and epsilon sarcoglycan disrupts the cardiac dystrophin complex

Alessio Lancioni, Ida Luisa Rotundo, Yvonne Monique Kobayashi, Luca D'Orsi, Stefania Aurino, Gerardo Nigro, Giulio Piluso, Dario Acampora, Mafalda Cacciottolo, Kevin P. Campbell, Vincenzo Nigro

Research output: Contribution to journalArticle

Abstract

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 Sgcenull 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.

Original languageEnglish
Article numberddr398
Pages (from-to)4644-4654
Number of pages11
JournalHuman Molecular Genetics
Volume20
Issue number23
DOIs
Publication statusPublished - Dec 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

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    Lancioni, A., Rotundo, I. L., Kobayashi, Y. M., D'Orsi, L., Aurino, S., Nigro, G., Piluso, G., Acampora, D., Cacciottolo, M., Campbell, K. P., & Nigro, V. (2011). Combined deficiency of alpha and epsilon sarcoglycan disrupts the cardiac dystrophin complex. Human Molecular Genetics, 20(23), 4644-4654. [ddr398]. https://doi.org/10.1093/hmg/ddr398