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
StatePublished - Jan 2000
Externally publishedYes

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Sarcoglycans
Genes
Smooth Muscle
Skeletal Muscle
Blood Vessels
Myocardium
Dystroglycans
Membranes
Striated Muscle
Muscular Dystrophies
Diaphragm
Type 2E Limb-girdle muscular dystrophy
Cardiomyopathies
Vascular Smooth Muscle
Necrosis
Kidney
Mutation

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Durbeej, M., Conn, R. D., Hrstka, R. F., Moore, S. A., Allamand, V., Davidson, B. L., ... 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.

Disruption of the β-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E. / Durbeej, Madeleine; Conn, Ronald D.; Hrstka, Ronald F.; Moore, Steven A.; Allamand, Valérie; Davidson, Beverly L.; Williamson, Roger A.; Campbell, Kevin P.

In: Molecular Cell, Vol. 5, No. 1, 01.2000, p. 141-151.

Research output: Contribution to journalArticle

Durbeej, M, Conn, RD, Hrstka, RF, Moore, SA, Allamand, V, Davidson, BL, Williamson, RA & Campbell, KP 2000, 'Disruption of the β-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E', Molecular Cell, vol. 5, no. 1, pp. 141-151.
Durbeej M, Conn RD, Hrstka RF, Moore SA, Allamand V, Davidson BL et al. Disruption of the β-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E. Molecular Cell. 2000 Jan;5(1):141-151.
Durbeej, Madeleine ; Conn, Ronald D. ; Hrstka, Ronald F. ; Moore, Steven A. ; Allamand, Valérie ; Davidson, Beverly L. ; Williamson, Roger A. ; Campbell, Kevin P. / Disruption of the β-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E. In: Molecular Cell. 2000 ; Vol. 5, No. 1. pp. 141-151.
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