Heat Failure Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight into Mechanism of Dilated Cardiomyopathy

Sci Rep. 2017 Dec 12;7(1):17417. doi: 10.1038/s41598-017-17572-y.


The pathogenesis of heart failure associated with dilated cardiomyopathy (DCM) may result in part from adenosine triphosphate (ATP) dysregulation in the myocardium. Under these conditions, diabetes-associated protein in insulin-sensitive tissue (DAPIT), which is encoded by the upregulated during skeletal muscle growth 5 (USMG5) gene, plays a crucial role in energy production by mitochondrial ATP synthase. To determine whether USMG5 is related to the development of heart failure, we performed clinical and experimental studies. Microarray analysis showed that the expression levels of USMG5 were positively correlated with those of natriuretic peptide precursor A in the human failed myocardium. When endogenous z-usmg5 in zebrafish was disrupted using morpholino (MO) oligonucleotides, the pericardial sac and atrial areas were larger and ventricular fractional shortening was reduced compared to in the control MO group. The expression levels of natriuretic peptides were upregulated in the z-usmg5 MO group compared to in controls. Further, microarray analysis revealed that genes in the calcium signalling pathway were downregulated in the z-usmg5 MO group. These results demonstrate that DAPIT plays a crucial role in the development of heart failure associated with DCM and thus may be a therapeutic target for heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / metabolism
  • Cardiomyopathy, Dilated / metabolism*
  • Cardiomyopathy, Dilated / pathology
  • Gene Expression
  • Gene Knockdown Techniques
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Humans
  • Mitochondrial Proton-Translocating ATPases / genetics
  • Mitochondrial Proton-Translocating ATPases / metabolism*
  • Mitochondrial Proton-Translocating ATPases / physiology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology*


  • ATP5MK protein, human
  • NPPA protein, human
  • Zebrafish Proteins
  • Atrial Natriuretic Factor
  • Mitochondrial Proton-Translocating ATPases
  • atp5md protein, zebrafish