Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1782296741966512128 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3870918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT johnsonnathanm thehdacinhibitortsaamelioratesazebrafishmodelofduchennemusculardystrophy AT farrgisth thehdacinhibitortsaamelioratesazebrafishmodelofduchennemusculardystrophy AT maveslisa thehdacinhibitortsaamelioratesazebrafishmodelofduchennemusculardystrophy AT johnsonnathanm hdacinhibitortsaamelioratesazebrafishmodelofduchennemusculardystrophy AT farrgisth hdacinhibitortsaamelioratesazebrafishmodelofduchennemusculardystrophy AT maveslisa hdacinhibitortsaamelioratesazebrafishmodelofduchennemusculardystrophy |