The renal distal convoluted tubule (DCT) is critical for the fine-tuning of urinary ion excretion and the control of blood pressure. Ion transport along the DCT is tightly controlled by posttranscriptional mechanisms including a complex interplay of kinases, phosphatases, and ubiquitin ligases. Previous work identified the transcription factor Prox-1 as a gene significantly enriched in the DCT of adult mice. To test if Prox-1 contributes to the transcriptional regulation of DCT function and structure, we developed a novel mouse model (NCC^cre:Prox-1^flox/flox) for an inducible deletion of Prox-1 specifically in the DCT. The deletion of Prox-1 had no obvious impact on DCT structure and growth independent whether the deletion was achieved in newborn or adult mice. Furthermore, DCT-specific Prox-1 deficiency did not alter DCT-proliferation in response to loop diuretic treatment. Likewise, the DCT-specific deletion of Prox-1 did not cause other gross phenotypic abnormalities. Body weight, urinary volume, Na⁺ and K⁺ excretion as well as plasma Na⁺, K⁺, and aldosterone levels were similar in Prox-1_DCT^KO and Prox-1_DCT^Ctrl mice. However, Prox-1_DCT^KO mice exhibited a significant hypomagnesemia with a profound downregulation of the DCT-specific apical Mg²⁺ channel TRPM6 and the NaCl cotransporter (NCC) at both mRNA and protein levels. The expression of other proteins involved in distal tubule Mg²⁺ and Na⁺ handling was not affected. Thus, Prox-1 is a DCT-enriched transcription factor that does not control DCT growth but contributes to the molecular control of DCT-dependent Mg²⁺ homeostasis in the adult kidney.

肾远曲小管 (DCT) 对于微调尿离子排泄和控制血压至关重要。沿着 DCT 的离子运输受到转录后机制的严格控制，包括激酶、磷酸酶和泛素连接酶的复杂相互作用。先前的工作将转录因子 Prox-1 鉴定为在成年小鼠的 DCT 中显着富集的基因。为了测试 Prox-1 是否有助于 DCT 功能和结构的转录调节，我们开发了一种新的小鼠模型（NCC ^cre :Prox-1 ^flox/flox) 用于在 DCT 中特异性地诱导 Prox-1 缺失。Prox-1 的缺失对 DCT 结构和生长没有明显影响，无论是在新生小鼠还是成年小鼠中实现的缺失。此外，DCT 特异性 Prox-1 缺乏不会改变响应袢利尿剂治疗的 DCT 增殖。同样，Prox-1 的 DCT 特异性缺失不会导致其他严重的表型异常。Prox-1 _DCT ^KO和 Prox-1 _DCT ^Ctrl小鼠的体重、尿量、Na ⁺和 K ⁺排泄以及血浆 Na ⁺、K ⁺和醛固酮水平相似。然而，Prox-1 _DCT ^KO小鼠表现出显着的低镁血症，在 mRNA 和蛋白质水平上，DCT 特异性顶端 Mg ²⁺通道 TRPM6 和 NaCl 协同转运蛋白 (NCC)显着下调。参与远端小管 Mg ²⁺和 Na ⁺处理的其他蛋白质的表达不受影响。因此，Prox-1 是一种富含 DCT 的转录因子，它不控制 DCT 生长，但有助于成人肾脏中 DCT 依赖性 Mg ²⁺稳态的分子控制。