Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics

Abstract Intramuscular injection and electroporation of naked plasmid DNA (IMEP) has emerged as a potential alternative to viral vector injection for transgene expression into skeletal muscles. In this study, IMEP was used to express the DUX4 gene into mouse tibialis anterior muscle. DUX4 is normall...

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Autores principales:	Aline Derenne, Alexandra Tassin, Thuy Hang Nguyen, Estelle De Roeck, Vincianne Jenart, Eugénie Ansseau, Alexandra Belayew, Frédérique Coppée, Anne-Emilie Declèves, Alexandre Legrand
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de019a5459f549d595a0412b6acbd90b
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spelling	oai:doaj.org-article:de019a5459f549d595a0412b6acbd90b2021-12-02T15:39:39ZInduction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics10.1038/s41598-020-68135-72045-2322https://doaj.org/article/de019a5459f549d595a0412b6acbd90b2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68135-7https://doaj.org/toc/2045-2322Abstract Intramuscular injection and electroporation of naked plasmid DNA (IMEP) has emerged as a potential alternative to viral vector injection for transgene expression into skeletal muscles. In this study, IMEP was used to express the DUX4 gene into mouse tibialis anterior muscle. DUX4 is normally expressed in germ cells and early embryo, and silenced in adult muscle cells where its pathological reactivation leads to Facioscapulohumeral muscular dystrophy. DUX4 encodes a potent transcription factor causing a large deregulation cascade. Its high toxicity but sporadic expression constitutes major issues for testing emerging therapeutics. The IMEP method appeared as a convenient technique to locally express DUX4 in mouse muscles. Histological analyses revealed well delineated muscle lesions 1-week after DUX4 IMEP. We have therefore developed a convenient outcome measure by quantification of the damaged muscle area using color thresholding. This method was used to characterize lesion distribution and to assess plasmid recirculation and dose–response. DUX4 expression and activity were confirmed at the mRNA and protein levels and through a quantification of target gene expression. Finally, this study gives a proof of concept of IMEP model usefulness for the rapid screening of therapeutic strategies, as demonstrated using antisense oligonucleotides against DUX4 mRNA.Aline DerenneAlexandra TassinThuy Hang NguyenEstelle De RoeckVincianne JenartEugénie AnsseauAlexandra BelayewFrédérique CoppéeAnne-Emilie DeclèvesAlexandre LegrandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aline Derenne Alexandra Tassin Thuy Hang Nguyen Estelle De Roeck Vincianne Jenart Eugénie Ansseau Alexandra Belayew Frédérique Coppée Anne-Emilie Declèves Alexandre Legrand Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics
description	Abstract Intramuscular injection and electroporation of naked plasmid DNA (IMEP) has emerged as a potential alternative to viral vector injection for transgene expression into skeletal muscles. In this study, IMEP was used to express the DUX4 gene into mouse tibialis anterior muscle. DUX4 is normally expressed in germ cells and early embryo, and silenced in adult muscle cells where its pathological reactivation leads to Facioscapulohumeral muscular dystrophy. DUX4 encodes a potent transcription factor causing a large deregulation cascade. Its high toxicity but sporadic expression constitutes major issues for testing emerging therapeutics. The IMEP method appeared as a convenient technique to locally express DUX4 in mouse muscles. Histological analyses revealed well delineated muscle lesions 1-week after DUX4 IMEP. We have therefore developed a convenient outcome measure by quantification of the damaged muscle area using color thresholding. This method was used to characterize lesion distribution and to assess plasmid recirculation and dose–response. DUX4 expression and activity were confirmed at the mRNA and protein levels and through a quantification of target gene expression. Finally, this study gives a proof of concept of IMEP model usefulness for the rapid screening of therapeutic strategies, as demonstrated using antisense oligonucleotides against DUX4 mRNA.
format	article
author	Aline Derenne Alexandra Tassin Thuy Hang Nguyen Estelle De Roeck Vincianne Jenart Eugénie Ansseau Alexandra Belayew Frédérique Coppée Anne-Emilie Declèves Alexandre Legrand
author_facet	Aline Derenne Alexandra Tassin Thuy Hang Nguyen Estelle De Roeck Vincianne Jenart Eugénie Ansseau Alexandra Belayew Frédérique Coppée Anne-Emilie Declèves Alexandre Legrand
author_sort	Aline Derenne
title	Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics
title_short	Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics
title_full	Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics
title_fullStr	Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics
title_full_unstemmed	Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics
title_sort	induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/de019a5459f549d595a0412b6acbd90b
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Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics

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