New publication in the journal Neuromuscular Disorders
Joachim
Berger, Silke
Berger, Thomas E.
Hall, Graham J. Lieschke, Peter D.
Currie
Neuromuscular Disorders (in press)
Abstract: Duchenne muscular dystrophy is caused by
mutations in the dystrophin gene. As in humans, zebrafish dystrophin is
initially expressed at the peripheral ends of the myofibres adjacent to
the myotendinous junction and gradually shifts to non-junctional sites.
Dystrophin-deficient zebrafish larvae are characterised by abundant
necrotic fibres being replaced by mono-nucleated infiltrates, extensive
fibrosis accompanied by inflammation, and a broader variation in muscle
fibre cross-sectional areas. Muscle progenitor proliferation cannot
compensate for the extensive skeletal muscle loss. Live imaging of
dystrophin-deficient zebrafish larvae documents detaching myofibres
elicited by muscle contraction. Correspondingly, the progressive
phenotype of dystrophin-deficient zebrafish resembles many aspects of
the human disease, suggesting that specific advantages of the zebrafish
model system, such as the ability to undertake in vivo drug screens and
real time analysis of muscle fibre loss, could be used to make novel
insights relevant to understanding and treating the pathological basis
of dystrophin deficient muscular dystrophy.
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