Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3
Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3
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DOI：
10.1074/jbc.m008664200
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发表时间：
2001-01-05
影响因子：
4.8
通讯作者：
Verkman, KS
中科院分区：
文献类型：
--
作者：
Yang, BX;Ma, TH;Verkman, KS
水通道蛋白（AQP）水通道AQP 3被认为是红细胞中主要的甘油和非AQP 1水转运蛋白，AQP 1和AQP 3也在肾脏中表达，在小鼠肾脏中它们的缺失产生不同形式的肾源性尿崩症。在这里，AQP 1/AQP 3双敲除小鼠的产生和分析，以研究AQP 3在红细胞和肾脏中的功能作用。从双杂合子小鼠的756只幼崽中出生了53只双敲除小鼠。与单基因敲除小鼠相比，双基因敲除小鼠的存活率降低，生长受损。AQP 1缺失使红细胞水渗透性降低7倍，但在AQP 1/AQP 3缺失小鼠中没有进一步降低。AQP 3缺失不影响红细胞甘油渗透性或根皮素对其的抑制作用，AQP 1/AQP 3双敲除小鼠的每日尿量（15 ml）是野生型小鼠的9倍，尿液渗透压（194 mosM）降低8.4倍。DDAVP给药或禁水后，小鼠保持多尿。大多数AQP 1/AQP 3基因敲除小鼠在4周龄时由于严重的多尿和肾积水而导致肾髓质萎缩和充满液体。我们的数据提供了直接的证据表明，AQP 3是不重要的功能，红细胞的水或甘油的渗透性，肾功能的研究表明，AQP 1和AQP 3的独立作用，在逆流交换和集合管渗透平衡，分别。
Aquaporin (AQP) water channel AQP3 has been proposed to be the major glycerol and non-AQP1 water transporter in erythrocytes, AQP1 and AQP3 are also expressed in the kidney where their deletion in mice produces distinct forms of nephrogenic diabetes insipidus. Here AQP1/AQP3 double knockout mice were generated and analyzed to investigate the functional role of AQP3 in erythrocytes and kidneys. 53 double knockout mice were born out of 756 pups from breeding double heterozygous mice. The double knockout mice had reduced survival and impaired growth compared with the single knockout mice. Erythrocyte water permeability was 7-fold reduced by AQP1 deletion but not further reduced in AQP1/AQP3 null mice. AQP3 deletion did not affect erythrocyte glycerol permeability or its inhibition by phloretin, Daily urine output in AQP1/AQP3 double knockout mice (15 ml) was 9-fold greater than in wildtype mice, and urine osmolality (194 mosM) was 8.4-fold reduced. The mice remained polyuric after DDAVP administration or water deprivation. The renal medulla in most AQP1/AQP3 null mice by age 4 weeks was atrophic and fluid-filled due to the severe polyuria and hydronephrosis. Our data provide direct evidence that AQP3 is not functionally important in erythrocyte water or glycerol permeability, The renal function studies indicate independent roles of AQP1 and AQP3 in countercurrent exchange and collecting duct osmotic equilibration, respectively.