急性基因敲除小鼠的Pendrin可降低其血压。
Acute genetic ablation of pendrin lowers blood pressure in mice.
作者信息
Trepiccione Francesco, Soukaseum Christelle, Baudrie Veronique, Kumai Yusuke, Teulon Jacques, Villoutreix Bruno, Cornière Nicolas, Wangemann Philine, Griffith Andrew J, Byung Choi Yoon, Hadchouel Juliette, Chambrey Regine, Eladari Dominique
机构信息
INSERM U970, Paris Cardiovascular Research Center, Université Paris-Descartes, Paris, France.
Hôpital Européen Georges Pompidou, Département de Physiologie, Assistance Publique-Hopitaux de Paris, Paris, France.
出版信息
Nephrol Dial Transplant. 2017 Jul 1;32(7):1137-1145. doi: 10.1093/ndt/gfw393.
BACKGROUND
Pendrin, the chloride/bicarbonate exchanger of β-intercalated cells of the renal connecting tubule and the collecting duct, plays a key role in NaCl reabsorption by the distal nephron. Therefore, pendrin may be important for the control of extracellular fluid volume and blood pressure.
METHODS
Here, we have used a genetic mouse model in which the expression of pendrin can be switched-on in vivo by the administration of doxycycline. Pendrin can also be rapidly removed when doxycycline administration is discontinued. Therefore, our genetic strategy allows us to test selectively the acute effects of loss of pendrin function.
RESULTS
We show that acute loss of pendrin leads to a significant decrease of blood pressure. In addition, acute ablation of pendrin did not alter significantly the acid-base status or blood K + concentration.
CONCLUSION
By using a transgenic mouse model, avoiding off-target effects related to pharmacological compounds, this study suggests that pendrin could be a novel target to treat hypertension.
背景
Pendrin是肾连接小管和集合管β-闰细胞中的氯离子/碳酸氢根离子交换体，在远端肾单位重吸收氯化钠过程中起关键作用。因此，Pendrin可能对细胞外液容量和血压的控制至关重要。
方法
在此，我们使用了一种基因小鼠模型，通过给予强力霉素可在体内开启Pendrin的表达。当停止给予强力霉素时，Pendrin也能迅速被清除。因此，我们的基因策略使我们能够选择性地测试Pendrin功能丧失的急性效应。
结果
我们发现Pendrin的急性缺失导致血压显著下降。此外，急性去除Pendrin对酸碱状态或血钾浓度没有显著影响。
结论
通过使用转基因小鼠模型，避免了与药理化合物相关的脱靶效应，本研究表明Pendrin可能是治疗高血压的新靶点。
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