The zebrafish dystrophic mutant softy maintains 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 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.
Jacoby
Arie S
AS
The Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
Busch-Nentwich
Elisabeth
E
Bryson-Richardson
Robert J
RJ
Hall
Thomas E
TE
Berger
Joachim
J
Berger
Silke
S
Sonntag
Carmen
C
Sachs
Caroline
C
Geisler
Robert
R
Stemple
Derek L
DL
Currie
Peter D
PD
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001485:Basement Membrane / Q000473:pathology; D002470:Cell Survival; D017931:DNA Primers / Q000235:genetics; D005123:Eye / Q000196:embryology; D006720:Homozygote; D007797:Laminin / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000196:embryology* / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D012508:Sarcolemma / Q000473:pathology; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology*
D017931:DNA Primers; D007797:Laminin; D029961:Zebrafish Proteins; C520014:laminin alpha2, zebrafish; C058783:laminin beta2