Defective membrane fusion and repair in Anoctamin5-deficient muscular dystrophy

Hum Mol Genet. 2016 May 15;25(10):1900-1911. doi: 10.1093/hmg/ddw063. Epub 2016 Feb 23.


Limb-girdle muscular dystrophies are a genetically diverse group of diseases characterized by chronic muscle wasting and weakness. Recessive mutations in ANO5 (TMEM16E) have been directly linked to several clinical phenotypes including limb-girdle muscular dystrophy type 2L and Miyoshi myopathy type 3, although the pathogenic mechanism has remained elusive. ANO5 is a member of the Anoctamin/TMEM16 superfamily that encodes both ion channels and regulators of membrane phospholipid scrambling. The phenotypic overlap of ANO5 myopathies with dysferlin-associated muscular dystrophies has inspired the hypothesis that ANO5, like dysferlin, may be involved in the repair of muscle membranes following injury. Here we show that Ano5-deficient mice have reduced capacity to repair the sarcolemma following laser-induced damage, exhibit delayed regeneration after cardiotoxin injury and suffer from defective myoblast fusion necessary for the proper repair and regeneration of multinucleated myotubes. Together, these data suggest that ANO5 plays an important role in sarcolemmal membrane dynamics. Genbank Mouse Genome Informatics accession no. 3576659.

Publication types

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

MeSH terms

  • Animals
  • Anoctamins
  • Chloride Channels / genetics*
  • Disease Models, Animal
  • Distal Myopathies / genetics*
  • Humans
  • Mice
  • Mice, Knockout
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / genetics*
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Muscular Dystrophies, Limb-Girdle / pathology
  • Mutation
  • Sarcolemma / pathology


  • ANO5 protein, human
  • Anoctamins
  • Chloride Channels

Supplementary concepts

  • Limb-girdle muscular dystrophy type 2A
  • Miyoshi Muscular Dystrophy 3