Generation of transgenic mice that conditionally express microRNA miR-145.
Generation of transgenic mice that conditionally express microRNA miR-145.
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DOI：
10.1002/dvg.23385
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Lilly B
中科院分区：
文献类型：
--
作者：
Sawant D;Klevenow E;Baeten JT;Thomas S;Manivannan S;Conway SJ;Lilly B
MicroRNA是细胞表型的调节剂，其功能有助于发育、稳态和疾病。miR-145是一种保守的microRNA，参与调节一系列表型。这些包括支持平滑肌分化、抑制干细胞多能性以及抑制肿瘤生长和转移。此前，我们的实验室证明miR-145通过抑制TGF-β信号通路来抑制心脏纤维化。miR-145对不同细胞类型的影响范围使其成为进一步研究的有吸引力的microRNA。在这里，我们描述了通过Cre重组酶介导的激活条件性表达miR-145的转基因小鼠的产生。单个创始细胞系的表征表明，miR-145在发育中的心血管系统中的过表达具有不利影响，其中三个独立的miR-145转基因细胞系表现出Cre依赖性致死性。表达分析表明，转基因的稳健表达，我们的分析揭示了一个新的下游目标的miR-145，Tnnt 2。miR-145转基因小鼠代表了一种有价值的工具，可以了解miR-145在不同细胞类型中的作用，并解决其作为治疗疾病的治疗介质的潜力。
MicroRNAs are modulators of cellular phenotypes and their functions contribute to development, homeostasis, and disease. miR-145 is a conserved microRNA that has been implicated in regulating an array of phenotypes. These include supporting smooth muscle differentiation, repression of stem cell pluripotency, and inhibition of tumor growth and metastasis. Previously, our lab demonstrated that miR-145 acts to suppress cardiac fibrosis through inhibition of the TGF-β signaling pathway. The range of effects that miR-145 has on different cell types makes it an attractive microRNA for further study. Here we describe the generation of transgenic mice that conditionally express miR-145 through Cre recombinase-mediated activation. Characterization of individual founder lines indicates that overexpression of miR-145 in the developing cardiovascular system has detrimental effects, with three independent miR-145 transgenic lines exhibited Cre-dependent lethality. Expression analysis demonstrates that the transgene is robustly expressed and our analysis reveals a novel downstream target of miR-145, Tnnt2. The miR-145 transgenic mice represent a valuable tool to understand the role of miR-145 in diverse cell types and to address its potential as a therapeutic mediator for the treatment of disease.
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