Our understanding of urinary concentrating and diluting mechanisms at the end of the 20th century was based largely on data from renal micropuncture studies, isolated perfused tubule studies, tissue analysis studies and anatomical studies, combined with mathematical modeling. Despite extensive data, several key questions remained to be answered. With the advent of the 21st century, a new approach, transgenic and knockout mouse technology, is providing critical new information about urinary concentrating processes. The central goal of this review is to summarize findings in transgenic and knockout mice pertinent to our understanding of the urinary concentrating mechanism, focusing chiefly on mice in which expression of specific renal transporters or receptors has been deleted. These include the major renal water channels (aquaporins), urea transporters, ion transporters and channels (NHE3, NKCC2, NCC, ENaC, ROMK, ClC-K1), G protein-coupled receptors (type 2 vasopressin receptor, prostaglandin receptors, endothelin receptors, angiotensin II receptors), and signaling molecules. These studies shed new light on several key questions concerning the urinary concentrating mechanism including: 1) elucidation of the role of water absorption from the descending limb of Henle in countercurrent multiplication, 2) an evaluation of the feasibility of the passive model of Kokko-Rector and Stephenson, 3) explication of the role of inner medullary collecting duct urea transport in water conservation, 4) an evaluation of the role of tubuloglomerular feedback in maintenance of appropriate distal delivery rates for effective regulation of urinary water excretion, and 5) elucidation of the importance of water reabsorption in the connecting tubule versus the collecting duct for maintenance of water balance.

中文翻译：

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新千年的小鼠模型和尿液浓缩机制。

我们对 20 世纪末尿液浓缩和稀释机制的理解主要基于肾脏显微穿刺研究、离体灌注小管研究、组织分析研究和解剖学研究的数据，并结合数学建模。尽管有大量数据，但仍有几个关键问题有待回答。随着 21 世纪的到来，一种新方法，即转基因和基因敲除小鼠技术，正在提供有关尿液浓缩过程的重要新信息。本综述的中心目标是总结与我们对尿液浓缩机制的理解相关的转基因和基因敲除小鼠的发现，主要关注特定肾脏转运蛋白或受体表达已被删除的小鼠。这些包括主要的肾水通道（水通道蛋白），尿素转运蛋白、离子转运蛋白和通道（NHE3、NKCC2、NCC、ENaC、ROMK、ClC-K1）、G 蛋白偶联受体（2 型加压素受体、前列腺素受体、内皮素受体、血管紧张素 II 受体）和信号分子。这些研究揭示了有关尿液浓缩机制的几个关键问题，包括：1) 阐明 Henle 降支吸水在逆流增殖中的作用，2) 评估 Kokko-Rector 被动模型的可行性和斯蒂芬森，3) 说明内髓集合管尿素运输在保水中的作用，4) 评估管状球反馈在维持适当的远端输送速率以有效调节尿水排泄中的作用，