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01-06-2019 | Myotonic Dystrophy | Original Article

Abnormal nuclear aggregation and myotube degeneration in myotonic dystrophy type 1

Authors: Yanlin Wang, Lei Hao, Hui Li, John D. Cleary, Michael P. Tomac, Arjun Thapa, Xiuming Guo, Desmond Zeng, Hongcai Wang, MacKezie McRae, Olivia Jastrzemski, Ali Marichen Smith-Fassler, Yuming Xu, Guangbin Xia

Published in: Neurological Sciences | Issue 6/2019

Abstract

Myotonic dystrophy type 1 (DM1) is caused by CTG nucleotide repeat expansions in the 3′-untranslated region (3′-UTR) of the dystrophia myotonica protein kinase (DMPK) gene. The expanded CTG repeats encode toxic CUG RNAs that cause disease, largely through RNA gain-of-function. DM1 is a fatal disease characterized by progressive muscle wasting, which has no cure. Regenerative medicine has emerged as a promising therapeutic modality for DM1, especially with the advancement of induced pluripotent stem (iPS) cell technology and therapeutic genome editing. However, there is an unmet need to identify in vitro outcome measures to demonstrate the therapeutic effects prior to in vivo clinical trials. In this study, we examined the muscle regeneration (myotube formation) in normal and DM1 myoblasts in vitro to establish outcome measures for therapeutic monitoring. We found normal proliferation of DM1 myoblasts, but abnormal nuclear aggregation during the early stage myotube formation, as well as myotube degeneration during the late stage of myotube formation. We concluded that early abnormal nuclear aggregation and late myotube degeneration offer easy and sensitive outcome measures to monitor therapeutic effects in vitro.

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Title: Abnormal nuclear aggregation and myotube degeneration in myotonic dystrophy type 1
Authors: Yanlin Wang
Lei Hao
Hui Li
John D. Cleary
Michael P. Tomac
Arjun Thapa
Xiuming Guo
Desmond Zeng
Hongcai Wang
MacKezie McRae
Olivia Jastrzemski
Ali Marichen Smith-Fassler
Yuming Xu
Guangbin Xia
Publication date: 01-06-2019
Publisher: Springer International Publishing
Keywords: Myotonic Dystrophy
Myotonic Dystrophy
Published in: Neurological Sciences / Issue 6/2019
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-019-03783-w

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Abnormal nuclear aggregation and myotube degeneration in myotonic dystrophy type 1

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