Department of Pediatrics, Child Health Research Center, University of Virginia, Charlottesville, Virginia, United States.
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Am J Physiol Renal Physiol. 2024 Sep 1;327(3):F489-F503. doi: 10.1152/ajprenal.00129.2024. Epub 2024 Jul 11.
Fate mapping and genetic manipulation of renin cells have relied on either noninducible lines that can introduce the developmental effects of gene deletion or bacterial artificial chromosome transgene-based inducible models that may be prone to spurious and/or ectopic gene expression. To circumvent these problems, we generated an inducible mouse model in which is under the control of the endogenous gene, an independent marker of renin cells that is expressed in a few extrarenal tissues. We confirmed the proper expression of using ; mice in which Akr1b7/renin cells become green fluorescent protein (GFP) upon tamoxifen administration. In embryos and neonates, GFP was found in juxtaglomerular cells, along the arterioles, and in the mesangium, and in adults, GFP was present mainly in juxtaglomerular cells. In mice treated with captopril and a low-salt diet to induce recruitment of renin cells, GFP extended along the afferent arterioles and in the mesangium. We generated mice to conditionally delete renin in adult mice and found a marked reduction in kidney renin mRNA and protein and mean arterial pressure in mutant animals. When subjected to a homeostatic threat, mutant mice were unable to recruit renin cells. Most importantly, these mice developed concentric vascular hypertrophy ruling out potential developmental effects on the vasculature due to the lack of renin. We conclude that mice constitute an excellent model for the fate mapping of renin cells and for the spatial and temporal control of gene expression in renin cells. Fate mapping and genetic manipulation are important tools to study the identity of renin cells. Here, we report on a novel mouse model, , for the spatial and temporal regulation of gene expression in renin cells. is properly expressed in renin cells during development and in the adult under basal conditions and under physiological stress. Moreover, renin can be efficiently deleted in the adult, leading to the development of concentric vascular hypertrophy.
肾素细胞的命运图谱和遗传操作依赖于非诱导性的细胞系，这些细胞系可以引入基因缺失的发育效应，或者依赖于细菌人工染色体转基因的诱导模型，这些模型可能容易出现假阳性和/或异位基因表达。为了避免这些问题，我们生成了一种诱导型小鼠模型，其中 受内源性 基因的控制， 是肾素细胞的一个独立标志物，在一些肾外组织中表达。我们使用 来证实 的正确表达；在给予他莫昔芬后，Akr1b7/肾素细胞变成绿色荧光蛋白（GFP）的小鼠。在胚胎和新生儿中，GFP 发现于肾小球旁细胞、小动脉和系膜中，而在成年小鼠中，GFP 主要存在于肾小球旁细胞中。在给予卡托普利和低盐饮食以诱导肾素细胞募集的小鼠中，GFP 延伸到入球小动脉和系膜中。我们生成了 小鼠，以在成年小鼠中条件性地删除肾素，并发现突变动物的肾脏肾素 mRNA 和蛋白以及平均动脉压明显降低。当受到稳态威胁时，突变小鼠无法募集肾素细胞。最重要的是，这些小鼠发生了向心性血管肥大，排除了由于缺乏肾素而对血管造成潜在发育影响的可能性。我们得出结论， 小鼠是肾素细胞命运图谱和肾素细胞中基因表达时空控制的理想模型。命运图谱和遗传操作是研究肾素细胞特性的重要工具。在这里，我们报告了一种新型的 小鼠模型， ，用于肾素细胞中基因表达的时空调节。 在发育过程中和成年期的基础条件下以及在生理应激下， 在肾素细胞中得到了正确表达。此外，在成年期可以有效地删除肾素，导致向心性血管肥大的发展。
