Analysis of urine concentrating mechanisms using the CLC-K1 null mice.

ClC-K1是一种氯离子通道，负责跨上皮氯离子在肾脏Henle‘s环的细小上行支处的转运。这种氯化物被认为构成了肾脏内髓中尿液浓缩机制的逆流系统。我们产生了CLC-K1基因敲除小鼠，发现这些小鼠表现出肾源性糖尿病灵感(NDI)。然而，NDI的确切机制仍有待确定。在本研究中，我们测量了野生型和基因敲除小鼠的组织渗透压和内髓中的电解质含量。我们发现，氯转运系统的缺陷本身就影响了包括尿素和钠在内的渗透物质的整体积累。这证实了逆流系统在没有其单一成分的情况下是不起作用的，并首次证实了逆流系统在活体内确实起作用。我们还描述了CLC-K1在新生儿肾脏中表达的发育变化。此外，利用CLC-K1小鼠，我们可以精确地测定其在小鼠肾脏中密切相关的氯离子通道CLC-K2。

CLC-K1 is a chloride channel responsible for transepithelial chloride transport in the thin ascending limb of Henle's loop in the kidney. This chloride had been postulated to constitute a countercurrent system for urinary concentration mechanism in the inner medulla of the kidney. We generated the CLC-K1 knockout mice and found that the mice showed nephrogenic diabetes inspidus (NDI). However, exact mechanisms of NDI remained to be determined. In this study, we measured tissue osmolarity and electrolytes contents in the inner medulla of wild-type and the knockout mice. We found that the defect of a chloride transport system alone affected the overall accumulation of osmolar substances including urea and Na. This confirmed that a countercurrent system did not work without its single component, and verified for the first time that the countersystem really works in vivo.We also described the developmental changes of CLC-K1 expression in neonatal kidney. Moreover, using the CLC-K1 mice, we could precisely determine its closely related chloride channel, CLC-K2, in the mouse kidney.