Fluorescence and Bioluminescence Imaging of Angiogenesis in Flk1-Nano-lantern Transgenic Mice.
Fluorescence and Bioluminescence Imaging of Angiogenesis in Flk1-Nano-lantern Transgenic Mice.
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DOI：
10.1038/srep46597
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发表时间：
2017-04-20
影响因子：
4.6
通讯作者：
Ema M
中科院分区：
文献类型：
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作者：
Matsushita J;Inagaki S;Nishie T;Sakasai T;Tanaka J;Watanabe C;Mizutani KI;Miwa Y;Matsumoto K;Takara K;Naito H;Kidoya H;Takakura N;Nagai T;Takahashi S;Ema M
血管生成对正常发育和肿瘤生长都很重要。然而，血管生成的分子和细胞机制尚不完全清楚，部分原因是缺乏良好的动物模型进行成像。在这里，我们报告了一种新型的转基因(TG)小鼠的产生，它在胎儿肝激酶1(Flk1)的控制下表达生物发光报告蛋白Nano-lantern。Flk1-纳米灯笼BAC TG小鼠概括了在发育和肿瘤生长过程中内皮细胞和淋巴管内皮细胞内源性Flk1的表达。重要的是，Flk1纳米灯笼BAC TG小鼠的主动脉环内皮细胞的生物发光成像使我们能够观察到内皮细胞在18小时内发芽，而没有检测到任何光毒性。此外，Flk1纳米灯笼BAC TG小鼠在移植肿瘤的自由移动小鼠中实现了肿瘤血管生成的延时发光成像。因此，这个转基因小鼠系为研究生理和病理背景下的血管生成提供了一个独特的模型。
Angiogenesis is important for normal development as well as for tumour growth. However, the molecular and cellular mechanisms underlying angiogenesis are not fully understood, partly because of the lack of a good animal model for imaging. Here, we report the generation of a novel transgenic (Tg) mouse that expresses a bioluminescent reporter protein, Nano-lantern, under the control of Fetal liver kinase 1 (Flk1). Flk1-Nano-lantern BAC Tg mice recapitulated endogenous Flk1 expression in endothelial cells and lymphatic endothelial cells during development and tumour growth. Importantly, bioluminescence imaging of endothelial cells from the aortic rings of Flk1-Nano-lantern BAC Tg mice enabled us to observe endothelial sprouting for 18 hr without any detectable phototoxicity. Furthermore, Flk1-Nano-lantern BAC Tg mice achieved time-lapse luminescence imaging of tumour angiogenesis in freely moving mice with implanted tumours. Thus, this transgenic mouse line contributes a unique model to study angiogenesis within both physiological and pathological contexts.