Evaluation of exon-skipping strategies for Duchenne muscular dystrophy utilizing dystrophin-deficient zebrafish

J. Berger; S. Berger; A.S. Jacoby; S.D. Wilton; P.D. Currie

doi:10.1111/j.1582-4934.2011.01260.x

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Evaluation of exon-skipping strategies for Duchenne muscular dystrophy utilizing dystrophin-deficient zebrafish

Journal article

Open access

Peer reviewed

Evaluation of exon-skipping strategies for Duchenne muscular dystrophy utilizing dystrophin-deficient zebrafish

J. Berger, S. Berger, A.S. Jacoby, S.D. Wilton and P.D. Currie

Journal of Cellular and Molecular Medicine, Vol.15(12), pp.2643-2651

2011

DOI: https://doi.org/10.1111/j.1582-4934.2011.01260.x

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Abstract

Duchenne muscular dystophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene. By utilizing antisense oligonucleotides, splicing of the dystrophin transcript can be altered so that exons harbouring a mutation are excluded from the mature mRNA. Although this approach has been shown to be effective to restore partially functional dystrophin protein, the level of dystrophin protein that is necessary to rescue a severe muscle pathology has not been addressed. As zebrafish dystrophin mutants (dmd) resemble the severe muscle pathology of human patients, we have utilized this model to evaluate exon skipping. Novel dmd mutations were identified to enable the design of phenotype rescue studies via morpholino administration. Correlation of induced exon-skipping efficiency and the level of phenotype rescue suggest that relatively robust levels of exon skipping are required to achieve significant therapeutic ameliorations and that pre-screening analysis of exon-skipping drugs in zebrafish may help to more accurately predict clinical trials for therapies of DMD.

Details

Title: Evaluation of exon-skipping strategies for Duchenne muscular dystrophy utilizing dystrophin-deficient zebrafish
Authors/Creators: J. Berger (Author/Creator) - Australian Regenerative Medicine Institute
S. Berger (Author/Creator) - Australian Regenerative Medicine Institute
A.S. Jacoby (Author/Creator) - Victor Chang Cardiac Research Institute
S.D. Wilton (Author/Creator) - The University of Western Australia
P.D. Currie (Author/Creator) - Australian Regenerative Medicine Institute
Publication Details: Journal of Cellular and Molecular Medicine, Vol.15(12), pp.2643-2651
Publisher: Wiley
Identifiers: 991005541688807891
Copyright: © 2011 The Authors.
Murdoch Affiliation: Murdoch University; Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.255 Musculoskeletal Disorders; 1.255.628 Duchenne Muscular Dystrophy
Web Of Science research areas: Cell Biology; Medicine, Research & Experimental
ESI research areas: Molecular Biology & Genetics