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The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy

Zebrafish are an excellent model for Duchenne muscular dystrophy. In particular, zebrafish provide a system for rapid, easy, and low-cost screening of small molecules that can ameliorate muscle damage in dystrophic larvae. Here we identify an optimal anti-sense morpholino cocktail that robustly knoc...

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Detalles Bibliográficos
Autores principales: Johnson, Nathan M., Farr, Gist H., Maves, Lisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870918/
https://www.ncbi.nlm.nih.gov/pubmed/24459606
http://dx.doi.org/10.1371/currents.md.8273cf41db10e2d15dd3ab827cb4b027
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author Johnson, Nathan M.
Farr, Gist H.
Maves, Lisa
author_facet Johnson, Nathan M.
Farr, Gist H.
Maves, Lisa
author_sort Johnson, Nathan M.
collection PubMed
description Zebrafish are an excellent model for Duchenne muscular dystrophy. In particular, zebrafish provide a system for rapid, easy, and low-cost screening of small molecules that can ameliorate muscle damage in dystrophic larvae. Here we identify an optimal anti-sense morpholino cocktail that robustly knocks down zebrafish Dystrophin (<i>dmd</i>-MO). We use two approaches, muscle birefringence and muscle actin expression, to quantify muscle damage and show that the <i>dmd</i>-MO dystrophic phenotype closely resembles the zebrafish <i>dmd</i> mutant phenotype. We then show that the histone deacetylase (HDAC) inhibitor TSA, which has been shown to ameliorate the <i>mdx</i> mouse Duchenne model, can rescue muscle fiber damage in both <i>dmd</i>-MO and <i>dmd</i> mutant larvae. Our study identifies optimal morpholino and phenotypic scoring approaches for dystrophic zebrafish, further enhancing the zebrafish <i>dmd</i> model for rapid and cost-effective small molecule screening.
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spelling pubmed-38709182013-12-26 The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy Johnson, Nathan M. Farr, Gist H. Maves, Lisa PLoS Curr Animal Models Zebrafish are an excellent model for Duchenne muscular dystrophy. In particular, zebrafish provide a system for rapid, easy, and low-cost screening of small molecules that can ameliorate muscle damage in dystrophic larvae. Here we identify an optimal anti-sense morpholino cocktail that robustly knocks down zebrafish Dystrophin (<i>dmd</i>-MO). We use two approaches, muscle birefringence and muscle actin expression, to quantify muscle damage and show that the <i>dmd</i>-MO dystrophic phenotype closely resembles the zebrafish <i>dmd</i> mutant phenotype. We then show that the histone deacetylase (HDAC) inhibitor TSA, which has been shown to ameliorate the <i>mdx</i> mouse Duchenne model, can rescue muscle fiber damage in both <i>dmd</i>-MO and <i>dmd</i> mutant larvae. Our study identifies optimal morpholino and phenotypic scoring approaches for dystrophic zebrafish, further enhancing the zebrafish <i>dmd</i> model for rapid and cost-effective small molecule screening. Public Library of Science 2013-09-17 /pmc/articles/PMC3870918/ /pubmed/24459606 http://dx.doi.org/10.1371/currents.md.8273cf41db10e2d15dd3ab827cb4b027 Text en http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Animal Models
Johnson, Nathan M.
Farr, Gist H.
Maves, Lisa
The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy
title The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy
title_full The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy
title_fullStr The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy
title_full_unstemmed The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy
title_short The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy
title_sort hdac inhibitor tsa ameliorates a zebrafish model of duchenne muscular dystrophy
topic Animal Models
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870918/
https://www.ncbi.nlm.nih.gov/pubmed/24459606
http://dx.doi.org/10.1371/currents.md.8273cf41db10e2d15dd3ab827cb4b027
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