The phenotype of dysferlin-deficient mice is not rescued by adeno-associated virus-mediated transfer of anoctamin 5

Hum Gene Ther Clin Dev. 2013 Jun;24(2):65-76. doi: 10.1089/humc.2012.217. Epub 2013 May 30.


Mutations in dysferlin and anoctamin 5 are the cause of muscular disorders, with the main presentations as limb-girdle muscular dystrophy or Miyoshi type of distal myopathy. Both these proteins have been implicated in sarcolemmal resealing. On the basis of similarities in associated phenotypes and protein functions, we tested the hypothesis that ANO5 protein could compensate for dysferlin absence. We first defined that the main transcript of ANO5 expressed in skeletal muscle is the 22-exon full-length isoform, and we demonstrated that dysferlin-deficient (Dysf (prmd)) mice have lower Ano5 expression levels, an observation that further enhanced the rational of the tested hypothesis. We then showed that AAV-mediated transfer of human ANO5 (hANO5) did not lead to apparent toxicity in wild-type mice. Finally, we demonstrated that AAV-hANO5 injection was not able to compensate for dysferlin deficiency in the Dysf (prmd) mouse model or improve the membrane repair defect seen in the absence of dysferlin. Consequently, overexpressing hANO5 does not seem to provide a valuable therapeutic strategy for dysferlin deficiency.

MeSH terms

  • Animals
  • Anoctamins
  • Cell Line
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Dependovirus / genetics*
  • Down-Regulation
  • Dysferlin
  • Gene Transfer Techniques
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophies, Limb-Girdle / pathology
  • Muscular Dystrophies, Limb-Girdle / therapy*
  • Phenotype
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism


  • ANO5 protein, human
  • Anoctamins
  • Chloride Channels
  • Dysf protein, mouse
  • Dysferlin
  • Membrane Proteins
  • Protein Isoforms