PUBLICATION
A mutation in serca underlies motility dysfunction in accordion zebrafish
- Authors
- Gleason, M.R., Armisen, R., Verdecia, M.A., Sirotkin, H., Brehm, P., and Mandel, G.
- ID
- ZDB-PUB-041208-8
- Date
- 2004
- Source
- Developmental Biology 276(2): 441-451 (Journal)
- Registered Authors
- Sirotkin, Howard
- Keywords
- none
- MeSH Terms
-
- Animals
- Calcium/metabolism
- Calcium-Transporting ATPases/chemistry
- Calcium-Transporting ATPases/genetics*
- Calcium-Transporting ATPases/metabolism*
- Mutation
- In Situ Hybridization
- Phenotype
- Amino Acid Sequence
- Protein Structure, Tertiary
- Oligonucleotides, Antisense/genetics
- Oligonucleotides, Antisense/metabolism
- Swimming/physiology*
- Zebrafish/anatomy & histology
- Zebrafish/genetics
- Zebrafish/physiology*
- Molecular Sequence Data
- Muscle, Skeletal/cytology
- Muscle, Skeletal/physiology
- Humans
- Patch-Clamp Techniques
- Models, Molecular
- Muscle Contraction/physiology
- PubMed
- 15581877 Full text @ Dev. Biol.
Citation
Gleason, M.R., Armisen, R., Verdecia, M.A., Sirotkin, H., Brehm, P., and Mandel, G. (2004) A mutation in serca underlies motility dysfunction in accordion zebrafish. Developmental Biology. 276(2):441-451.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping