Characterisation of the regenerative response in a zebrafish model of Duchenne Muscular Dystrophy

Funded Activity Summary

Muscular Dystrophy is the most common lethal inherited disorder of children. Within dystrophic patients skeletal muscle fibres undergo cycles of muscle breakdown and regeneration until the regenerative response is exhausted, leading to a progressive muscle wasting. Regeneration of skeletal muscle is controlled by a specialised set of stem cells termed satellite cells that are activated to produce new muscle fibres in response to injury. As such satellite cells have been the targets of intense investigation for the development of cell based therapies for muscular dystrophies. We have developed a new vertebrate animal system in which to analyse muscular dystrophy and the control of satellite cell function, the zebrafish. We have shown that a mutation in a gene responsible for causing Duchenne Muscular Dystrophy in humans also causes a similar disease in Zebrafish. Zebrafish are an embryologically and genetically tractable model system in which to study muscle cell biology. The ability to visualise muscle growth within an optically transparent embryo and larvae, coupled with a large number of mutations affecting muscle patterning and growth suggest that it is a suitable model to explore muscle maintenance. The specific aims of this proposal are to determine in our new dystrophic zebrafish model, how regeneration controls the onset and pathology of muscle fibre loss. We wish to determine if muscle stems cells analogous to those known to function in mammalian muscle can be detected in zebrafish in normal and dystrophic muscle. We then plan to identify novel genes controlling muscle growth and regeneration through the genetic and embryological advantages that zebrafish as a model organism provide. We hope this will lead to a better understanding of how muscle stem cells are generated and are activated in muscular dystrophy and we hope this will open new avenues for muscle stem cell based therapies of the disease.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $435,750.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Developmental Genetics (incl. Sex Determination)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Genetics | Muscle | Muscle Development | Muscle Regeneration | Muscular Dystrophy | Regeneration | Stem Cell Therapy | Stem Cells

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