期刊
CIRCULATION
卷 118, 期 15, 页码 1567-1576出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.108.769984
关键词
Dicer; genetics; heart failure; microRNA
资金
- European Society of Cardiology [912-04-054, 912-04-017]
- Netherlands Organization for Health Research and Development [917-863-72]
- Netherlands Heart Foundation [NHS2007B167]
- European Union [LSHM-CT2005-018833/EUGeneHeart]
Background-Dicer, an RNAse III endonuclease critical for processing of pre-microRNAs ( miRNAs) into mature 22-nucleotide miRNAs, has proven a useful target to dissect the significance of miRNAs biogenesis in mammalian biology. Methods and Results-To circumvent the embryonic lethality associated with germline null mutations for Dicer, we triggered conditional Dicer loss through the use of a tamoxifen-inducible Cre recombinase in the postnatal murine myocardium. Targeted Dicer deletion in 3-week-old mice provoked premature death within 1 week accompanied by mild ventricular remodeling and dramatic atrial enlargement. In the adult myocardium, loss of Dicer induced rapid and dramatic biventricular enlargement, accompanied by myocyte hypertrophy, myofiber disarray, ventricular fibrosis, and strong induction of fetal gene transcripts. Comparative miRNA profiling revealed a set of miRNAs that imply causality between miRNA depletion and spontaneous cardiac remodeling. Conclusions-Overall, these results indicate that modifications in miRNA biogenesis affect both juvenile and adult myocardial morphology and function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据