Dystrophin is required for the formation of stable muscle attachments in the zebrafish embryo

Bassett, D.I., Bryson-Richardson, R.J., Daggett, D.F., Gautier, P., Kennan, D.G., and Currie, P.D.
Development (Cambridge, England)   130(23): 5851-5860 (Journal)
Registered Authors
Bassett, David, Bryson-Richardson, Robert, Currie, Peter D., Daggett, Dave
myomuscular junctions, myotendinous junctions, dystrophin, sapje, muscle attachments, muscular dystrophy, congenital myopathy
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Humans
  • Macromolecular Substances
  • Membrane Proteins/classification
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Molecular Sequence Data
  • Muscle Fibers, Skeletal/metabolism*
  • Muscle Fibers, Skeletal/pathology
  • Muscle Fibers, Skeletal/ultrastructure
  • Muscle Proteins/classification
  • Muscle Proteins/genetics
  • Muscle Proteins/metabolism*
  • Muscular Dystrophy, Duchenne/genetics
  • Muscular Dystrophy, Duchenne/metabolism
  • Phenotype
  • Phylogeny
  • Recombinant Fusion Proteins/genetics
  • Recombinant Fusion Proteins/metabolism
  • Sarcolemma/metabolism
  • Sequence Alignment
  • Transgenes
  • Zebrafish/anatomy & histology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/classification
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
14573513 Full text @ Development
A class of recessive lethal zebrafish mutations has been identified in which normal skeletal muscle differentiation is followed by a tissue-specific degeneration that is reminiscent of the human muscular dystrophies. Here, we show that one of these mutations, sapje, disrupts the zebrafish orthologue of the X-linked human Duchenne muscular dystrophy (DMD) gene. Mutations in this locus cause Duchenne or Becker muscular dystrophies in human patients and are thought to result in a dystrophic pathology through disconnecting the cytoskeleton from the extracellular matrix in skeletal muscle by reducing the level of dystrophin protein at the sarcolemma. This is thought to allow tearing of this membrane, which in turn leads to cell death. Surprisingly, we have found that the progressive muscle degeneration phenotype of sapje mutant zebrafish embryos is caused by the failure of embryonic muscle end attachments. Although a role for dystrophin in maintaining vertebrate myotendinous junctions (MTJs) has been postulated previously and MTJ structural abnormalities have been identified in the Dystrophin-deficient mdx mouse model, in vivo evidence of pathology based on muscle attachment failure has thus far been lacking. This zebrafish mutation may therefore provide a model for a novel pathological mechanism of Duchenne muscular dystrophy and other muscle diseases.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes