A mutation in serca underlies motility dysfunction in accordion zebrafish

Dev Biol. 2004 Dec 15;276(2):441-51. doi: 10.1016/j.ydbio.2004.09.008.

Abstract

Zebrafish acquire the ability for fast swimming early in development. The motility mutant accordion (acc) undergoes exaggerated and prolonged contractions on both sides of the body, interfering with the acquisition of patterned swimming responses. Our whole cell recordings from muscle indicate that the defect is not manifested in neuromuscular transmission. However, imaging of skeletal muscle of larval acc reveals greatly prolonged calcium transients and associated contractions in response to depolarization. Positional cloning of acc identified a serca mutation as the cause of the acc phenotype. SERCA is a sarcoplasmic reticulum transmembrane protein in skeletal muscle that mediates calcium re-uptake from the myoplasm. The mutation in SERCA, a serine to phenylalanine substitution, is likely to result in compromised protein function that accounts for the observed phenotype. Indeed, direct evidence that mutant SERCA causes the motility dysfunction was provided by the finding that wild type fish injected with an antisense morpholino directed against serca, exhibited accordion-like contractions and impaired swimming. We conclude that the motility dysfunction in embryonic and larval accordion zebrafish stems directly from defective calcium transport in skeletal muscle rather than defective CNS drive.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Calcium-Transporting ATPases / chemistry
  • Calcium-Transporting ATPases / genetics*
  • Calcium-Transporting ATPases / metabolism*
  • Humans
  • In Situ Hybridization
  • Models, Molecular
  • Molecular Sequence Data
  • Muscle Contraction / physiology
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology
  • Mutation
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Patch-Clamp Techniques
  • Phenotype
  • Protein Structure, Tertiary
  • Swimming / physiology*
  • Zebrafish / anatomy & histology
  • Zebrafish / genetics
  • Zebrafish / physiology*

Substances

  • Oligonucleotides, Antisense
  • Calcium-Transporting ATPases
  • Calcium