The zebrafish dystrophic mutantsoftymaintains muscle fibre viability despite basement membrane rupture and muscle detachment
The zebrafish dystrophic mutantsoftymaintains muscle fibre viability despite basement membrane rupture and muscle detachment
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 β2 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.
- Monash University Australia
- University of Queensland Australia
- Wellcome Sanger Institute United Kingdom
- Max Planck Institute for Developmental Biology Germany
- Government of Victoria Australia
Laminin beta 2, Basement membrane, 571, Cell Survival, Molecular Sequence Data, Muscle Fibers, Skeletal, Skeletal muscle, Eye, Basement Membrane, 1309 Developmental Biology, Animals, Genetically Modified, Sarcolemma, 1312 Molecular Biology, Animals, Amino Acid Sequence, Zebrafish, DNA Primers, Base Sequence, Sequence Homology, Amino Acid, Homozygote, Muscular Dystrophy, Animal, Zebrafish Proteins, Muscular dystrophy, Mutation, Laminin
Laminin beta 2, Basement membrane, 571, Cell Survival, Molecular Sequence Data, Muscle Fibers, Skeletal, Skeletal muscle, Eye, Basement Membrane, 1309 Developmental Biology, Animals, Genetically Modified, Sarcolemma, 1312 Molecular Biology, Animals, Amino Acid Sequence, Zebrafish, DNA Primers, Base Sequence, Sequence Homology, Amino Acid, Homozygote, Muscular Dystrophy, Animal, Zebrafish Proteins, Muscular dystrophy, Mutation, Laminin
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