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 exhibiting 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.

中文翻译：

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条件性表达 microRNA miR-145 的转基因小鼠的产生。


MicroRNA 是细胞表型的调节剂，其功能有助于发育、体内平衡和疾病。 miR-145是一种保守的 microRNA，与一系列表型的调节有关。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值得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。各个创始品系的表征表明，发育中的心血管系统中miR-145的过度表达具有有害影响，三个独立的miR-145转基因品系表现出 Cre 依赖性致死性。表达分析表明转基因稳定表达，我们的分析揭示了miR-145的一个新下游靶标Tnnt2 。 miR-145转基因小鼠是了解miR-145在不同细胞类型中的作用并探讨其作为疾病治疗介质的潜力的宝贵工具。