Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels
Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels
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DOI：
10.1074/jbc.274.29.20071
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发表时间：
1999-07-16
影响因子：
4.8
通讯作者：
Verkman, AS
中科院分区：
文献类型：
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作者：
Ma, TH;Song, YL;Verkman, AS
水通道蛋白-6（Aquaporin-6，AQP 5）是一种水选择性转运蛋白，表达于唾液腺浆液性腺泡上皮细胞。我们通过靶向基因破坏产生AQP 5缺失小鼠。基因型分布从intercross的创始人AQP 5杂合子小鼠为70：69：29野生型：杂合子：敲除，表明受损的产前生存的null小鼠。基因敲除小鼠外观大体正常，但在断奶后喂食固体食物时，生长速度比同窝匹配的野生型小鼠慢20%。在AQP 5基因敲除小鼠中，毛果芸香碱刺激的唾液产生减少了60%以上。与野生型小鼠的唾液相比，基因敲除小鼠的唾液高渗（420 mosM）且粘稠度明显更高。淀粉酶和蛋白质分泌，唾液粘液细胞的功能，不受AQP 5缺失。水通道AQP 1和AQP 4也定位于唾液腺;然而，毛果芸香碱刺激研究显示AQP 1和AQP 4敲除小鼠的唾液体积或组成没有缺陷。这些结果暗示了AQP 5在唾液分泌中的关键作用，并提供了直接的证据表明，高上皮细胞膜透水性是主动的，近等渗液体运输所必需的。
Aquaporin-6 (AQP5) is a water selective transporting protein expressed in epithelial cells of serous acini in salivary gland. We generated AQP5 null mice by targeted gene disruption. The genotype distribution from intercross of founder AQP5 heterozygous mice was 70: 69:29 wild-type:heterozygote:knockout, indicating impaired prenatal survival of the null mice. The knockout mice had grossly normal appearance, but grew similar to 20% slower than litter-matched wild-type mice when placed on solid food after weaning. Pilocarpine-stimulated saliva production was reduced by more than 60% in AQP5 knockout mice. Compared with the saliva from wild-type mice, the saliva from knockout mice was hypertonic (420 mosM) and dramatically more viscous. Amylase and protein secretion, functions of salivary mucous cells, were not affected by AQP5 deletion. Water channels AQP1 and AQP4 have also been localized to salivary gland; however, pilocarpine stimulation studies showed no defect in the volume or composition of saliva in AQP1 and AQP4 knockout mice. These results implicate a key role for AQP5 in saliva fluid secretion and provide direct evidence that high epithelial cell membrane water permeability is required for active, near-isosmolar fluid transport.