PUBLICATION

The zebrafish dystrophic mutant softy maintains muscle fibre viability despite basement membrane rupture and muscle detachment

Authors
Jacoby, A.S., Busch-Nentwich, E., Bryson-Richardson, R.J., Hall, T.E., Berger, J., Berger, S., Sonntag, C., Sachs, C., Geisler, R., Stemple, D.L., and Currie, P.D.
ID
ZDB-PUB-090914-39
Date
2009
Source
Development (Cambridge, England)   136(19): 3367-3376 (Journal)
Registered Authors
Berger, Joachim, Bryson-Richardson, Robert, Busch-Nentwich, Elisabeth, Currie, Peter D., Geisler, Robert, Hall, Thomas, Jacoby, Arie, Sachs, Caroline, Sonntag, Carmen, Stemple, Derek L.
Keywords
Skeletal muscle, Zebrafish, Laminin β2, Basement membrane, Muscular dystrophy
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Basement Membrane/pathology
  • Cell Survival
  • DNA Primers/genetics
  • Eye/embryology
  • Homozygote
  • Laminin/genetics*
  • Laminin/physiology*
  • Molecular Sequence Data
  • Muscle Fibers, Skeletal/pathology
  • Muscular Dystrophy, Animal/embryology*
  • Muscular Dystrophy, Animal/genetics*
  • Muscular Dystrophy, Animal/pathology
  • Mutation*
  • Sarcolemma/pathology
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology*
PubMed
19736328 Full text @ Development
Abstract
The skeletal muscle basement membrane fulfils several crucial functions during development and in the mature myotome and defects in its composition underlie certain forms of muscular dystrophy. A major component of this extracellular structure is the laminin polymer, which assembles into a resilient meshwork that protects the sarcolemma during contraction. Here we describe a zebrafish mutant, softy, which displays severe embryonic muscle degeneration as a result of initial basement membrane failure. The softy phenotype is caused by a mutation in the lamb2 gene, identifying laminin beta2 as an essential component of this basement membrane. Uniquely, softy homozygotes are able to recover and survive to adulthood despite the loss of myofibre adhesion. We identify the formation of ectopic, stable basement membrane attachments as a novel means by which detached fibres are able to maintain viability. This demonstration of a muscular dystrophy model possessing innate fibre viability following muscle detachment suggests basement membrane augmentation as a therapeutic strategy to inhibit myofibre loss.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes