ZFIN ID: ZDB-PUB-040810-6
Small Heart Mutation Reveals Novel Roles of Na+/K+-ATPase in Maintaining Ventricular Cardiomyocyte Morphology and Viability in Zebrafish
Yuan, S., and Joseph, E.M.
Date: 2004
Source: Circulation research   95(6): 595-603 (Journal)
Registered Authors: Joseph, Elaine, Yuan, Shipeng
Keywords: none
MeSH Terms:
  • Abnormalities, Drug-Induced/embryology
  • Abnormalities, Multiple/embryology
  • Abnormalities, Multiple/enzymology
  • Abnormalities, Multiple/genetics
  • Animals
  • Apoptosis/genetics
  • Brain/abnormalities
  • Brain/embryology
  • Crosses, Genetic
  • Eye Abnormalities/chemically induced
  • Eye Abnormalities/embryology
  • Eye Abnormalities/genetics
  • Genes, Lethal
  • Genotype
  • Heart/embryology
  • Heart Defects, Congenital/embryology
  • Heart Defects, Congenital/enzymology
  • Heart Defects, Congenital/genetics
  • Kidney/abnormalities
  • Kidney/embryology
  • Morphogenesis/genetics
  • Morpholines/pharmacology
  • Morpholines/toxicity
  • Mutagenesis
  • Myocytes, Cardiac/drug effects
  • Myocytes, Cardiac/enzymology
  • Myocytes, Cardiac/ultrastructure
  • Oligodeoxyribonucleotides, Antisense/pharmacology
  • Oligodeoxyribonucleotides, Antisense/toxicity
  • Otolithic Membrane/abnormalities
  • Otolithic Membrane/embryology
  • Ouabain/pharmacology
  • Ouabain/toxicity
  • Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase/deficiency
  • Sodium-Potassium-Exchanging ATPase/genetics
  • Sodium-Potassium-Exchanging ATPase/physiology*
  • Tail/abnormalities
  • Tail/embryology
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 15297381 Full text @ Circ. Res.
ABSTRACT
Forward genetic screens in zebrafish have been used to identify mutations in genes with important roles in organogenesis. One of these mutants, small heart, develops a diminutive and severely malformed heart and multiple developmental defects of the brain, ears, eyes, and kidneys. Using a positional cloning approach, we identify that the mutant gene encodes the zebrafish Na(+)/K(+)-ATPase alpha1B1 protein. Disruption of Na(+)/K(+)-ATPase alpha1B1 function via morpholino "knockdown" or pharmacological inhibition with ouabain phenocopies the mutant phenotype, in a dose-dependent manner. Heterozygosity for the mutation sensitizes embryos to ouabain treatment. Our findings present novel genetic and morphological details on the function of the Na(+)/K(+)-ATPase alpha1B1 in early cardiac morphogenesis and the pathogenesis of the small heart malformation. We demonstrate that the reduced size of the mutant heart is caused by dysmorphic ventricular cardiomyocytes and an increase in ventricular cardiomyocyte apoptosis. This study provides a new insight that Na(+)/K(+)-ATPase alpha1B is required for maintaining ventricular cardiomyocyte morphology and viability.
ADDITIONAL INFORMATION