Disruption of the β-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E

Madeleine Durbeej, Ronald D. Conn, Ronald F. Hrstka, Steven A. Moore, Valérie Allamand, Beverly L. Davidson, Roger A. Williamson, Kevin P. Campbell

Research output: Contribution to journalArticle

Abstract

Limb-girdle muscular dystrophy type 2E (LGMD 2E) is caused by mutations in the β-sarcoglycan gene, which is expressed in skeletal, cardiac, and smooth muscle. β-sarcoglycan-deficient (Sgcb-null) mice developed severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. The sarcoglycan-sarcospan and dystroglycan complexes were disrupted in skeletal, cardiac, and smooth muscle membranes. ε-sarcoglycan was also reduced in membrane preparations of striated and smooth muscle. Loss of the sarcoglycan-sarcospan complex in vascular smooth muscle resulted in vascular irregularities in heart, diaphragm, and kidneys. Further biochemical characterization suggested the presence of a distinct ε-sarcoglycan complex in skeletal muscle that was disrupted in Sgcb-null mice. Thus, perturbation of vascular function together with disruption of the ε-sarcoglycan-containing complex represents a novel mechanism in the pathogenesis of LGMD 2E.

Original languageEnglish (US)
Pages (from-to)141-151
Number of pages11
JournalMolecular cell
Volume5
Issue number1
DOIs
StatePublished - Jan 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Durbeej, M., Conn, R. D., Hrstka, R. F., Moore, S. A., Allamand, V., Davidson, B. L., Williamson, R. A., & Campbell, K. P. (2000). Disruption of the β-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E. Molecular cell, 5(1), 141-151. https://doi.org/10.1016/S1097-2765(00)80410-4