Journal Article

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 and Vincenzo Nigro

in Human Molecular Genetics

Volume 20, issue 23, pages 4644-4654
Published in print December 2011 | ISSN: 0964-6906
Published online September 2011 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddr398

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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, ɛ-SG, may compensate for α-SG deficiency in the heart. To investigate the function of ɛ-SG in striated muscle, we generated an Sgce-null mouse and a Sgca-;Sgce-null mouse, which lacks both α- and ɛ-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 ɛ-SG is important in preventing cardiomyopathy in α-SG deficiency.

Journal Article.  5583 words.  Illustrated.

Subjects: Genetics and Genomics

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