Mdx Mouse Model
Researchers across the globe have utilized various animal models to study DMD. The most common animal model used to study therapeutics for DMD is the mdx mouse owing to its low cost and easy accessibility. The mdx mouse, has a nonsense mutation in exon 23 of the Dmd gene that leads to complete loss of the dystrophin protein 12, 13. The mdx mouse model of DMD is not considered an ideal model for understanding the pathogenesis of DMD owing to significant differences in physiology from humans and display of milder phenotypes compared to DMD patients. The diaphragm muscle of the mdx mouse however, exhibits a pattern of degeneration, fibrosis and severe functional deficit comparable to that of human DMD limb muscle14 and is often the muscle
…show more content…
The sapje locus was identified as dmd, the zebrafish orthologue of the human DMD gene and mutations at the sapje locus abolish the dystrophin orthologue in zebrafish 37, 38. Sapje zebrafish mutants have a recessive, lethal, nonsense mutation that results in a premature stop codon in the dystrophin gene (on chromosome 1). The resulting phenotype is the embryonic-onset, progressive degeneration of skeletal muscle in the sap homozygous zebrafish. Embryonically, the mechanism of degeneration occurs due to the detachment of somitic myofibers from the myosepta, the tendon-like sheets of ECM. In the zebrafish larvae, this muscle fiber detachment is visible at the myotendinous junctions and is accompanied by extensive degeneration, fibrosis, inflammatory responses and activation of muscle fiber regeneration, reminiscent of the severe pathological phenotype observed in human DMD 39. This makes the zebrafish animal model a powerful tool that can be used to assess the effect of therapeutics for DMD. There are several benefits of using zebrafish for highthroughput whole-organism screening of chemical libraries. Firstly, the mutant zebrafish progeny are easy to obtain in large numbers and can be easily treated with different chemicals in multi-well plates to determine if disease progression can be
The sapje locus was identified as dmd, the zebrafish orthologue of the human DMD gene and mutations at the sapje locus abolish the dystrophin orthologue in zebrafish 37, 38. Sapje zebrafish mutants have a recessive, lethal, nonsense mutation that results in a premature stop codon in the dystrophin gene (on chromosome 1). The resulting phenotype is the embryonic-onset, progressive degeneration of skeletal muscle in the sap homozygous zebrafish. Embryonically, the mechanism of degeneration occurs due to the detachment of somitic myofibers from the myosepta, the tendon-like sheets of ECM. In the zebrafish larvae, this muscle fiber detachment is visible at the myotendinous junctions and is accompanied by extensive degeneration, fibrosis, inflammatory responses and activation of muscle fiber regeneration, reminiscent of the severe pathological phenotype observed in human DMD 39. This makes the zebrafish animal model a powerful tool that can be used to assess the effect of therapeutics for DMD. There are several benefits of using zebrafish for highthroughput whole-organism screening of chemical libraries. Firstly, the mutant zebrafish progeny are easy to obtain in large numbers and can be easily treated with different chemicals in multi-well plates to determine if disease progression can be