Luminal valves of collecting lymphatic vessels are critical for maintaining unidirectional flow of lymph and their dysfunction underlies several forms of primary lymphedema. Here, we report on the generation of a transgenic mouse expressing the tamoxifen inducible CreER^T2 under the control of Cldn11 promoter that allows, for the first time, selective and temporally controlled targeting of lymphatic valve endothelial cells. We show that within the vasculature CLDN11 is specifically expressed in lymphatic valves but is not required for their development as mice with a global loss of Cldn11 display normal valves in the mesentery. Tamoxifen treated Cldn11-CreER^T2 mice also carrying a fluorescent Cre-reporter displayed reporter protein expression selectively in lymphatic valves and, to a lower degree, in venous valves. Analysis of developing vasculature further showed that Cldn11-CreER^T2-mediated recombination is induced during valve leaflet formation, and efficient labeling of valve endothelial cells was observed in mature valves. The Cldn11-CreER^T2 mouse thus provides a valuable tool for functional studies of valves.

中文翻译：

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用于选择性靶向淋巴瓣的诱导型 Cldn11-CreERT2 小鼠系

收集淋巴管的腔瓣对于维持淋巴液的单向流动至关重要，它们的功能障碍是几种原发性淋巴水肿的基础。在这里，我们报告了在Cldn11启动子控制下表达他莫昔芬诱导型CreER ^T2的转基因小鼠的产生，该启动子首次允许选择性和时间控制靶向淋巴瓣膜内皮细胞。我们表明，在脉管系统内，CLDN11 在淋巴瓣膜中特异性表达，但对于它们的发育来说并不是必需的，因为Cldn11 整体缺失的小鼠在肠系膜中显示出正常的瓣膜。他莫昔芬治疗Cldn11-CreER ^T2携带荧光 Cre-reporter 的小鼠在淋巴瓣中选择性地显示报告蛋白表达，在静脉瓣中的表达程度较低。对发育中的脉管系统的分析进一步表明，Cldn11-CreER ^T2介导的重组在瓣叶形成期间被诱导，并且在成熟瓣膜中观察到瓣膜内皮细胞的有效标记。Cldn11 - CreER ^T2鼠标因此为阀门的功能研究提供了宝贵的工具。