Alpha 7 integrin preserves the function of the extensor digitorum longus muscle in dystrophin-null mice

J Appl Physiol (1985). 2013 Nov 1;115(9):1388-92. doi: 10.1152/japplphysiol.00602.2013. Epub 2013 Aug 29.

Abstract

The dystrophin-associated glycoprotein complex (DGC) and the α7β1-integrin complex are two independent protein complexes that link the extracellular matrix with the cytoskeleton in muscle cells. These associations stabilize the sarcolemma during force transmission. Loss of either one of these complexes leads to muscular dystrophy. Dystrophin is a major component of the DGC. Its absence results in Duchenne muscular dystrophy (DMD). Because α7-integrin overexpression has been shown to ameliorate muscle histopathology in mouse models of DMD, we hypothesize that the α7β1-integrin complex can help preserve muscle function. To test this hypothesis, we evaluated muscle force, elasticity, and the viscous property of the extensor digitorum longus muscle in 19-day-old normal BL6, dystrophin-null mdx4cv, α7-integrin-null, and dystrophin/α7-integrin double knockout mice. While nominal changes were found in single knockout mice, contractility and passive properties were significantly compromised in α7-integrin double knockout mice. Our results suggest that DGC and α7β1-integrin complexes may compensate each other to maintain normal skeletal muscle function. α7β1-Integrin upregulation may hold promise to treat not only histological, but also physiological, defects in DMD.

Keywords: DMD; EDL muscle; contractile force; dystrophin; mdx4cv; muscular dystrophy; passive force; α7β1-integrin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Dystrophin / metabolism*
  • Integrin alpha Chains / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology*
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / physiopathology*

Substances

  • Antigens, CD
  • Dystrophin
  • Integrin alpha Chains
  • integrin alpha7