Presented at the Australian Physiological and Pharmacological Society Symposium Stretch-induced Muscle Damage in Sport and Disease, September 2003. The papers in these proceedings were peer reviewed under the supervision of the APPS Editor. The papers are being published with the permission of the APPS and were initially published on the APPS website (http://www.apps.org.au).
IDENTIFICATION OF A ZEBRAFISH MODEL OF MUSCULAR DYSTROPHY
Article first published online: 3 AUG 2004
Clinical and Experimental Pharmacology and Physiology
Volume 31, Issue 8, pages 537–540, August 2004
How to Cite
Bassett, D. and Currie, P. D. (2004), IDENTIFICATION OF A ZEBRAFISH MODEL OF MUSCULAR DYSTROPHY. Clinical and Experimental Pharmacology and Physiology, 31: 537–540. doi: 10.1111/j.1440-1681.2004.04030.x
- Issue published online: 3 AUG 2004
- Article first published online: 3 AUG 2004
- Received 28 October 2003; revision 11 March 2004; accepted 20 May 2004.
- muscular dystrophy;
1. Large-scale mutagenic screens of the zebrafish genome have identified a number of different classes of mutations that disrupt skeletal muscle formation. Of particular interest and relevance to human health is a class of recessive lethal mutations in which muscle differentiation occurs normally, but is followed by tissue-specific degeneration reminiscent of human muscular dystrophies.
2. We have shown that one member of this class of mutations, sapje (sap), results from mutations within the zebrafish orthologue of the 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 by disrupting the link between the actin cytoskeleton and the extracellular matrix in skeletal muscle cells.
3. We have found that the progressive muscle degeneration phenotype of sapje-mutant zebrafish embryos is caused by the failure of somitic muscle attachments at the embryonic myotendinous junction (MTJ).
4. Although a role for dystrophin at the MTJ 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 is thus far lacking. Therefore, the sapjre mutation may provide a model for a novel pathological mechanism of Duchenne muscular dystrophy and other muscle diseases. In the present review, we discuss this finding in light of previously postulated models of dystrophin function.