Impaired urea accumulation in the inner medulla of mice lacking the urea transporter UT-A2
Impaired urea accumulation in the inner medulla of mice lacking the urea transporter UT-A2
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DOI：
10.1128/mcb.25.16.7357-7363.2005
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发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Sasaki, S
中科院分区：
文献类型：
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作者：
Uchida, S;Sohara, E;Sasaki, S
尿素转运蛋白UT-A2是短袢肾单位中Henle袢的细降支的主要尿素转运蛋白，它参与了髓质中的尿素再循环，从而产生浓缩尿。为了研究UT-A2在体内的生理作用，我们通过删除UT-A2启动子来产生UT-A2选择性敲除小鼠。Western分析，免疫组化和定量逆转录-PCR被用来确认特定的UT-A2缺失与其他UT-A转运蛋白的保存。与野生型小鼠相比，在正常条件下或脱水情况下，未观察到摄入正常蛋白质饮食（20%蛋白质）的UT-A2（-/-）小鼠的尿量差异。同样，未观察到UT-A2（-/-）小鼠髓质内尿素蓄积受损。然而，在低蛋白饮食（4%蛋白质）中，与野生型同窝小鼠相比，在脱水UT-A2（-/-）小鼠中观察到最大尿渗透压浓度显著降低（分别为2，500 mosmol vs 3，450 mosmol）。在UT-A2（-/-）小鼠中也观察到内髓质中尿素蓄积显著减少;然而，未观察到Na+和Cl-蓄积差异。因此，UT-A2对于在肾脏的尿素供应受限时维持内髓中的高浓度尿素是重要的。
Urea transporter UT-A2, the major urea transporter of the thin descending limb of the loop of Henle in short loop nephrons, has been implicated in urea recycling in the medulla, thereby producing concentrated urine. To investigate the physiological role of UT-A2 in vivo, we generated UT-A2-selective knockout mice by deleting the UT-A2 promoter. Western analysis, immunohistochemistry, and quantitative reverse transcription-PCR were used to confirm the specific deletion of UT-A2 with preservation of other UT-A transporters. Compared to wild-type mice, differences in the urine outputs of UT-A2(-/-) mice consuming a normal protein diet (20% protein) were not observed under normal conditions or with dehydration. Likewise, impairment of urea accumulation in the inner medulla of UT-A2(-/-) mice was not observed. On a low-protein diet (4% protein), however, significantly reduced maximal urine osmolality was observed in dehydrated UT-A2(-/-) mice compared to wild-type littermates (2,500 mosmol versus 3,450 mosmol, respectively). A significant reduction in urea accumulation in the inner medulla was also observed in UT-A2(-/-) mice; however, differences in Na+ and Cl- accumulation were not observed. Thus, UT-A2 is important for maintaining a high concentration of urea in the inner medulla when urea supply to the kidney is limited.