A mutation in serca underlies motility dysfunction in accordion zebrafish

Michelle R. Gleason, Ricardo Armisen, Mark A. Verdecia, Howard Sirotkin, Paul Brehm, Gail Mandel

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)441-451
Number of pages11
JournalDevelopmental Biology
Volume276
Issue number2
DOIs
StatePublished - Dec 15 2004
Externally publishedYes

Fingerprint

Zebrafish
Skeletal Muscle
Calcium
Mutation
Phenotype
Morpholinos
Sarcoplasmic Reticulum
Patch-Clamp Techniques
Phenylalanine
Serine
Organism Cloning
Fishes
Proteins
Muscles

Keywords

  • Calcium
  • Mapping
  • Motility
  • Muscle
  • Mutant
  • SERCA
  • Structure
  • Zebrafish

ASJC Scopus subject areas

  • Developmental Biology

Cite this

A mutation in serca underlies motility dysfunction in accordion zebrafish. / Gleason, Michelle R.; Armisen, Ricardo; Verdecia, Mark A.; Sirotkin, Howard; Brehm, Paul; Mandel, Gail.

In: Developmental Biology, Vol. 276, No. 2, 15.12.2004, p. 441-451.

Research output: Contribution to journalArticle

Gleason, Michelle R. ; Armisen, Ricardo ; Verdecia, Mark A. ; Sirotkin, Howard ; Brehm, Paul ; Mandel, Gail. / A mutation in serca underlies motility dysfunction in accordion zebrafish. In: Developmental Biology. 2004 ; Vol. 276, No. 2. pp. 441-451.
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