In vivo characterization of human myofibrillar myopathy genes in zebrafish

Biochem Biophys Res Commun. 2015 May 29;461(2):217-23. doi: 10.1016/j.bbrc.2015.03.149. Epub 2015 Apr 9.


Myofibrillar myopathies (MFM) are progressive diseases of human heart and skeletal muscle with a severe impact on life quality and expectancy of affected patients. Although recently several disease genes for myofibrillar myopathies could be identified, today most genetic causes and particularly the associated mechanisms and signaling events that lead from the mutation to the disease phenotype are still mostly unknown. To assess whether the zebrafish is a suitable model system to validate MFM candidate genes using targeted antisense-mediated knock-down strategies, we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally. Consistently, targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure. Similar to what was shown in MFM patients, MFM gene-deficient zebrafish showed pronounced gene-specific phenotypic and structural differences. In summary, our results indicate that the zebrafish is a suitable model to functionally and structurally evaluate novel MFM disease genes in vivo.

Keywords: Cardiac muscle; Myofibrillar myopathy; Reverse genetics; Skeletal muscle; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Genetic Predisposition to Disease
  • Heart Failure / genetics
  • Heart Failure / pathology
  • Humans
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myopathies, Structural, Congenital / genetics
  • Myopathies, Structural, Congenital / pathology
  • Zebrafish / genetics*

Supplementary concepts

  • Myofibrillar Myopathy