Abnormal nuclear aggregation and myotube degeneration in myotonic dystrophy type 1.
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| Title: | Abnormal nuclear aggregation and myotube degeneration in myotonic dystrophy type 1. |
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| Authors: | Wang, Yanlin (AUTHOR), Hao, Lei (AUTHOR), Li, Hui (AUTHOR), Cleary, John D. (AUTHOR), Tomac, Michael P. (AUTHOR), Thapa, Arjun (AUTHOR), Guo, Xiuming (AUTHOR), Zeng, Desmond (AUTHOR), Wang, Hongcai (AUTHOR), McRae, MacKezie (AUTHOR), Jastrzemski, Olivia (AUTHOR), Smith-Fassler, Ali Marichen (AUTHOR), Xu, Yuming (AUTHOR), Xia, Guangbin (AUTHOR) |
| Source: | Neurological Sciences. Jun2019, Vol. 40 Issue 6, p1255-1265. 11p. 6 Color Photographs, 2 Black and White Photographs, 3 Graphs. |
| Subjects: | Myotonia atrophica, Degeneration (Pathology), Protein kinases, Genome editing, Muscle regeneration, Skeletal muscle physiology, In vitro studies, Skeletal muscle, Research funding, Cell physiology, Regeneration (Biology), Cell culture, Cell nuclei, Animal experimentation, Stem cells |
| 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. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| 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. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 15901874 |
| DOI: | 10.1007/s10072-019-03783-w |
