title: A mutation in serca underlies motility dysfunction in accordion zebrafish.
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.
authors.affiliation: Department of Neurobiology and Behavior, State University of New York at Stony Brook, 550 CMM, Stony Brook, NY 11794, USA. mryu@ic.sunysb.edu
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Gleason
authors.forename: Ricardo
authors.initials: R
authors.lastname: Armisen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Verdecia
authors.forename: Howard
authors.initials: H
authors.lastname: Sirotkin
authors.forename: Paul
authors.initials: P
authors.lastname: Brehm
authors.forename: Gail
authors.initials: G
authors.lastname: Mandel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010641:Phenotype; D017434:Protein Structure, Tertiary; D013550:Swimming / Q000502:physiology*; D015027:Zebrafish / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*
chemical_list: D016376:Oligonucleotides, Antisense; D000252:Calcium-Transporting ATPases; D002118:Calcium