Ma T, Song Y, Gillespie A, Carlson E J, Epstein C J, Verkman A S
Departments of Medicine, Physiology, and Pediatrics, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
J Biol Chem. 1999 Jul 16;274(29):20071-4. doi: 10.1074/jbc.274.29.20071.
Aquaporin-5 (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 approximately 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.
水通道蛋白5（AQP5）是一种水选择性转运蛋白，在唾液腺浆液性腺泡的上皮细胞中表达。我们通过靶向基因敲除构建了AQP5基因敲除小鼠。奠基者AQP5杂合小鼠杂交后代的基因型分布为野生型:杂合子:敲除型 = 70:69:29，表明基因敲除小鼠的产前存活率受损。基因敲除小鼠外观基本正常，但断奶后食用固体食物时，其生长速度比同窝对照野生型小鼠慢约20%。毛果芸香碱刺激引起的唾液分泌在AQP5基因敲除小鼠中减少了60%以上。与野生型小鼠的唾液相比，基因敲除小鼠的唾液为高渗性（420 mosM）且黏度显著更高。唾液黏液细胞的功能，即淀粉酶和蛋白质分泌，不受AQP5缺失的影响。水通道蛋白1（AQP1）和水通道蛋白4（AQP4）也定位于唾液腺；然而，毛果芸香碱刺激研究表明，AQP1和AQP4基因敲除小鼠的唾液量或成分无缺陷。这些结果表明AQP5在唾液分泌中起关键作用，并提供了直接证据，证明活跃的近等渗液体转运需要高上皮细胞膜水通透性。
