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

使用 CLC-K1 缺失小鼠分析尿液浓缩机制。

• 批准号: 12671028
• 负责人: UCHIDA Shinichi
• 金额: $ 2.11万
• 依托单位: TOKYO MEDEICAL AND DENTAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671028/
• 关键词: chloride Channel; counter current system; knockout mice; 尿濃縮

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.

CLC-K1是一种氯离子通道，负责肾脏亨利氏袢的细升支中的跨上皮氯离子转运。这种氯化物被假定为构成肾脏内髓中尿浓缩机制的逆流系统。我们产生了CLC-K1基因敲除小鼠，发现小鼠表现出肾源性糖尿病（NDI）。然而，NDI的确切机制仍有待确定。在这项研究中，我们测量了组织渗透压和电解质含量的野生型和基因敲除小鼠的内髓。我们发现，单独的氯离子转运系统的缺陷会影响包括尿素和钠在内的渗透压物质的总体积累。这证实了一个逆流系统没有它的单一组成部分，并验证了第一次在体内的反系统确实工作。我们还描述了CLC-K1在新生儿肾脏表达的发育变化。此外，使用CLC-K1小鼠，我们可以精确地确定其密切相关的氯离子通道，CLC-K2，在小鼠肾脏。

项目成果

K. Kobayashi: "Introrenal and cellular localization of CLC-K2 protein in the mouse kidney"J. Am. Soo. Nephrol.. 12. 1327-1334 (2001)

K. Kobayashi：“小鼠肾脏中 CLC-K2 蛋白的肾内和细胞定位”J。

Kida Y: "Locolization of Mouse CLC-6 and CLC7 mRNA and their functional compkementation of yeost CLC gene mutant"Histochem Cell Biol. 115(3). 189-194 (2001)

Kida Y：“小鼠 CLC-6 和 CLC7 mRNA 的定位及其对酵母 CLC 基因突变体的功能补充”Histochem Cell Biol。

A.Hayama: "Isolation and characterization of the human CLC-5 chloride channel gene promoter"Gene. 261. 355-364 (2000)

A.Hayama：“人 CLC-5 氯离子通道基因启动子的分离和表征”基因。

S. Uchida: "In vivo rote of CLC chloride channels in the kidney"Am. J. Physiol. 279. F802-F808 (2000)

S. Uchida：“肾脏中 CLC 氯离子通道的体内死记”Am。

Uchida,S: "In vivo role of CLC chloride channel in the Kidney"Am.J.Physiol. 279. F802-F808 (2000)

Uchida,S：“CLC 氯离子通道在肾脏中的体内作用”Am.J.Physiol。