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A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy

Duchenne muscular dystrophy (DMD) is a life-threatening neuromuscular disease caused by the lack of dystrophin, resulting in progressive muscle wasting and locomotor dysfunctions. By adulthood, almost all patients also develop cardiomyopathy, which is the primary cause of death in DMD. Although ther...

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Autores principales: Wong, Tatianna Wai Ying, Ahmed, Abdalla, Yang, Grace, Maino, Eleonora, Steiman, Sydney, Hyatt, Elzbieta, Chan, Parry, Lindsay, Kyle, Wong, Nicole, Golebiowski, Diane, Schneider, Joel, Delgado-Olguín, Paul, Ivakine, Evgueni A., Cohn, Ronald D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522028/
https://www.ncbi.nlm.nih.gov/pubmed/32988972
http://dx.doi.org/10.1242/dmm.045369
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author Wong, Tatianna Wai Ying
Ahmed, Abdalla
Yang, Grace
Maino, Eleonora
Steiman, Sydney
Hyatt, Elzbieta
Chan, Parry
Lindsay, Kyle
Wong, Nicole
Golebiowski, Diane
Schneider, Joel
Delgado-Olguín, Paul
Ivakine, Evgueni A.
Cohn, Ronald D.
author_facet Wong, Tatianna Wai Ying
Ahmed, Abdalla
Yang, Grace
Maino, Eleonora
Steiman, Sydney
Hyatt, Elzbieta
Chan, Parry
Lindsay, Kyle
Wong, Nicole
Golebiowski, Diane
Schneider, Joel
Delgado-Olguín, Paul
Ivakine, Evgueni A.
Cohn, Ronald D.
author_sort Wong, Tatianna Wai Ying
collection PubMed
description Duchenne muscular dystrophy (DMD) is a life-threatening neuromuscular disease caused by the lack of dystrophin, resulting in progressive muscle wasting and locomotor dysfunctions. By adulthood, almost all patients also develop cardiomyopathy, which is the primary cause of death in DMD. Although there has been extensive effort in creating animal models to study treatment strategies for DMD, most fail to recapitulate the complete skeletal and cardiac disease manifestations that are presented in affected patients. Here, we generated a mouse model mirroring a patient deletion mutation of exons 52-54 (Dmd Δ52-54). The Dmd Δ52-54 mutation led to the absence of dystrophin, resulting in progressive muscle deterioration with weakened muscle strength. Moreover, Dmd Δ52-54 mice present with early-onset hypertrophic cardiomyopathy, which is absent in current pre-clinical dystrophin-deficient mouse models. Therefore, Dmd Δ52-54 presents itself as an excellent pre-clinical model to evaluate the impact on skeletal and cardiac muscles for both mutation-dependent and -independent approaches.
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spelling pubmed-75220282020-09-29 A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy Wong, Tatianna Wai Ying Ahmed, Abdalla Yang, Grace Maino, Eleonora Steiman, Sydney Hyatt, Elzbieta Chan, Parry Lindsay, Kyle Wong, Nicole Golebiowski, Diane Schneider, Joel Delgado-Olguín, Paul Ivakine, Evgueni A. Cohn, Ronald D. Dis Model Mech Research Article Duchenne muscular dystrophy (DMD) is a life-threatening neuromuscular disease caused by the lack of dystrophin, resulting in progressive muscle wasting and locomotor dysfunctions. By adulthood, almost all patients also develop cardiomyopathy, which is the primary cause of death in DMD. Although there has been extensive effort in creating animal models to study treatment strategies for DMD, most fail to recapitulate the complete skeletal and cardiac disease manifestations that are presented in affected patients. Here, we generated a mouse model mirroring a patient deletion mutation of exons 52-54 (Dmd Δ52-54). The Dmd Δ52-54 mutation led to the absence of dystrophin, resulting in progressive muscle deterioration with weakened muscle strength. Moreover, Dmd Δ52-54 mice present with early-onset hypertrophic cardiomyopathy, which is absent in current pre-clinical dystrophin-deficient mouse models. Therefore, Dmd Δ52-54 presents itself as an excellent pre-clinical model to evaluate the impact on skeletal and cardiac muscles for both mutation-dependent and -independent approaches. The Company of Biologists Ltd 2020-09-21 /pmc/articles/PMC7522028/ /pubmed/32988972 http://dx.doi.org/10.1242/dmm.045369 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Wong, Tatianna Wai Ying
Ahmed, Abdalla
Yang, Grace
Maino, Eleonora
Steiman, Sydney
Hyatt, Elzbieta
Chan, Parry
Lindsay, Kyle
Wong, Nicole
Golebiowski, Diane
Schneider, Joel
Delgado-Olguín, Paul
Ivakine, Evgueni A.
Cohn, Ronald D.
A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy
title A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy
title_full A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy
title_fullStr A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy
title_full_unstemmed A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy
title_short A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy
title_sort novel mouse model of duchenne muscular dystrophy carrying a multi-exonic dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522028/
https://www.ncbi.nlm.nih.gov/pubmed/32988972
http://dx.doi.org/10.1242/dmm.045369
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