Abnormal nuclear aggregation and myotube degeneration in myotonic dystrophy type 1.
Abnormal nuclear aggregation and myotube degeneration in myotonic dystrophy type 1.
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强直性肌营养不良 1 型异常核聚集和肌管变性。
DOI：
10.1007/s10072-019-03783-w
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Xia,Guangbin
中科院分区：
文献类型：
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作者：
Wang,Yanlin;Hao,Lei;Li,Hui;Cleary,JohnD;Tomac,MichaelP;Thapa,Arjun;Guo,Xiuming;Zeng,Desmond;Wang,Hongcai;McRae,MacKezie;Jastrzemski,Olivia;Smith-Fassler,AliMarichen;Xu,Yuming;Xia,Guangbin
强直性肌营养不良1型（DM 1）是由肌营养不良性肌强直蛋白激酶（DMPK）基因3′-非翻译区（3′-UTR）中CTG核苷酸重复扩增引起的。扩增的CTG重复序列编码毒性CUG RNA，其主要通过RNA功能获得引起疾病。DM 1是一种致命的疾病，其特征是进行性肌肉萎缩，无法治愈。再生医学已成为DM 1的一种有前途的治疗方式，特别是随着诱导多能干细胞（iPS）技术和治疗性基因组编辑的进步。然而，在体内临床试验之前确定体外结果测量以证明治疗效果的需求尚未得到满足。在这项研究中，我们研究了肌肉再生（肌管形成）在正常和DM 1成肌细胞在体外建立治疗监测的结果措施。我们发现DM 1成肌细胞的正常增殖，但在早期阶段的肌管形成的异常核聚集，以及在肌管形成的晚期阶段的肌管变性。我们的结论是，早期异常核聚集和晚期肌管变性提供了简单和敏感的结果措施，以监测体外治疗效果。
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.