A 1.3 kb promoter fragment confers spatial and temporal expression of utrophin A mRNA in mouse skeletal muscle fibers

被引:15
作者
Stocksley, MA
Chakkalakal, JV
Bradford, A
Miura, P
De Repentigny, Y
Kothary, R
Jasmin, BJ
机构
[1] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada
[2] Univ Ottawa, Ctr Neuromuscular Dis, Fac Med, Ottawa, ON K1H 8M5, Canada
[3] Ottawa Hosp, Ottawa Hlth Res Inst, Ottawa, ON K1H 8L6, Canada
基金
加拿大健康研究院;
关键词
Duchenne muscular dystrophy; utrophin; transgenic promoter reporter mouse; neuromuscular junction; muscle regeneration; postnatal development;
D O I
10.1016/j.nmd.2005.03.008
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Upregulation of utrophin in muscle is currently being examined as a potential therapy for Duchenne muscular dystrophy patients. In this context, we generated transgenic mice harboring a 1.3 kb human utrophin A promoter fragment driving expression of the lacZ gene. Characterization of reporter expression during postnatal muscle development revealed that the levels and localization of beta-galactosidase parallel expression of utrophin A transcripts. Moreover, we noted that the utrophin A promoter is more active in slow soleus muscles. Additionally, expression of the reporter gene was regulated during muscle regeneration in a manner similar to utrophin A transcripts. Together, these results show that the utrophin A promoter-lacZ construct mirrors expression of utrophin A mRNAs indicating that this utrophin A promoter fragment confers temporal and spatial patterns of expression in skeletal muscle. This transgenic mouse will be valuable as an in vivo model for developing and testing molecules aimed at increasing utrophin A expression. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:437 / 449
页数:13
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