Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice
Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice
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DOI：
10.1073/pnas.95.16.9660
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Verkman, AS
中科院分区：
文献类型：
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作者：
Schnermann, J;Chou, CL;Verkman, AS
为了研究水通道蛋白1（AQP 1）在近端小管功能中的作用，对AQP 1基因敲除小鼠进行了体外近端小管微灌注和体内微穿刺测量。通过靶向基因破坏产生敲除小鼠，并且先前发现敲除小鼠不能响应于缺水而浓缩它们的尿液。未麻醉的敲除小鼠消耗的液体比野生型小鼠多2.8倍，并且具有较低的尿液渗透压（505 +/-40对1081 +/-68毫渗）。AQP 1基因敲除[-/-]小鼠近端小管S2节段离体微灌注的跨上皮渗透水通透性（Pf）为0.033 +/- 0.005 cm/s（SE，it = 6只小鼠，37 ℃），远低于野生型[ +/+]小鼠小管的0.15 +/- 0.03 cm/s（n = 8）（P < 0.01）。在等渗管腔灌注液和浴溶液的存在下，（nl/min/mm小管长度）为0.31 ± 0.12（-/-，it = 5）和0.64 +/- 0.15（+/+，n = 8），通过自由流动显微穿刺测定，近端小管液中不渗透性标记物TF/P的小管液与血浆浓度的比值为1.36 ± 0.05（-/-，rt 8小鼠[53个小管]）和1.95 +/- 0.09（+/+，n = 7只小鼠[40个小管]）（P < 0.001），对应于滤过液负荷的26 +/- 3% [-/-]和48 +/- 2% [+/+]吸收。在远端小管液的收集中，TF/P分别为2.8 ± 0.3 [-/-]和4.4 ± 0.5 [+/+]，分别相当于62 ± 4% [-/-]和76 ± 3% [+/+]的吸收率（P < 0.02）。这些数据表明，AQP 1缺失导致小鼠近端小管透水性降低和液体吸收缺陷。因此，野生型小鼠近端小管的高透水性主要是跨细胞的，由AQP 1基质通道介导，并且是有效的近等渗液体吸收所需的。
To investigate the role of aquaporin-l (AQP1) water channels in proximal tubule function, in vitro proximal tubule microperfusion and in vivo micropuncture measurements were done on AQP1 knockout mice. The knock-out mice were generated by targeted gene disruption and found previously to be unable to concentrate their urine in response to water deprivation, Unanesthetized knockout mice consumed 2.8-fold more fluid than wild-type mice and had lower urine osmolality (505 +/- 40 vs. 1081 +/- 68 milliosmolar). Transepithelial osmotic water permeability (Pf) in isolated microperfused S2 segments of proximal tubule from AQP1 knockout [-/-] mice was 0.033 +/- 0.005 cm/s (SE, it = 6 mice, 37 degrees C), much lower than that of 0.15 +/- 0.03 cm/s (n = 8) in tubules from wild-type [ +/+] mice (P < 0.01). In the presence of isosmolar luminal perfusate and bath solutions, spontaneous fluid absorption rates (nl/min/mm tubule length) were 0.31 +/- 0.12 (-/-, it = 5) and 0.64 +/- 0.15 (+/+, n = 8), As determined by free-flow micropuncture, the ratios of tubular fluid-to-plasma concentrations of an impermeant marker TF/P in end proximal tubule fluid were 1.36 +/- 0.05 (-/-, rt 8 mice [53 tubules]) and 1.95 +/- 0.09 (+/+, n = 7 mice [40 tubules]) (P < 0.001), corresponding to 26 +/- 3% [-/-] and 48 +/- 2% [+/+] absorption of the filtered fluid load, In collections of distal tubule fluid, TF/P mere 2.8 +/- 0.3 [-/-] and 4.4 +/- 0.5 [+/+], corresponding to 62 +/- 4% [-/-] and 76 +/- 3% [+/+] absorption (P < 0.02), These data indicate that AQP1 deletion in mice results in decreased transepithelial proximal tubule water permeability and defective fluid absorption. Thus, the high water permeability in proximal tubule of wild-type mice is primarily transcellular, mediated by AQP1 mater channels, and required for efficient near-isosmolar fluid absorption.