The Functional Consequences of Dystrophin Deficiency in Skeletal Muscles

  • Jean-Marie Gillis
Chapter
Part of the Protein Reviews book series (PRON, volume 6)

Abstract

Duchenne muscular dystrophy (DMD) is caused by mutation(s) affecting the dystrophin gene that codes for a cytoskeletal protein. Dystrophin interacts with cytoskeletal actin filaments and with a complex of transmembrane glycoproteins. This assembly disintegrates when dystrophin is absent. The purpose of this chapter is to review the structural and functional disorders observed in dystrophin-deficient muscles in order to understand their role and evaluate their importance in the pathologic processes that eventually lead to fiber necrosis. A preliminary brief presentation outlines the main facts of DMD and its genetics in humans. As an enormous wealth of data have been obtained from studies of the mdx mouse, a natural mutant lacking dystrophin, an extensive description and analysis of the dystrophic phenotype of this animal model of DMD is presented. The review covers the fields of histology, regeneration, mechanics, electrophysiology, intracellular calcium homeostasis, protease activation, protein over/down expression, inflammatory response and microcirculation in mdx muscles. An attempt is made to distinguish between initial pathologic processes, thought to be specific to the lack of dystrophin, from downstream events. The loss of the mechanical strength of the fiber plasma membrane resulting from the lack of dystrophin and of its associated protein appears to be the primary defect responsible for initiating the pathologic cascade of muscle dystrophy. Consequences of this situation for the development of compensatory therapies is discussed.

Keywords

Satellite Cell Duchenne Muscular Dystrophy Duchenne Muscular Dystrophy Eccentric Contraction Dystrophin Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Jean-Marie Gillis
    • 1
  1. 1.Department of PhysiologyCatholic University of LouvainBruxellesBelgium

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