Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway.
Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17815-20. doi: 10.1073/pnas.1110655108. Epub 2011 Oct 11.
Tissue- and cell-specific deletion of the Aqp4 gene is required to differentiate between the numerous pools of aquaporin-4 (AQP4) water channels. A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood-brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence of a significant endothelial pool of AQP4. In agreement, immunofluorescence analysis of cryostate sections and quantitative immunogold analysis of ultrathin sections revealed no AQP4 signals in capillary endothelia. Compared with litter controls, glial-conditional Aqp4 knockout mice showed a 31% reduction in brain water uptake after systemic hypoosmotic stress and a delayed postnatal resorption of brain water. Deletion of astroglial Aqp4 did not affect the barrier function to macromolecules. Our data suggest that the blood-brain barrier (BBB) is more complex than anticipated. Notably, under certain conditions, the astrocyte covering of brain microvessels is rate limiting to water movement.
组织和细胞特异性的 Aqp4 基因缺失是区分大量水通道蛋白-4（AQP4）水通道所必需的。生成了一种胶质条件性 Aqp4 敲除小鼠品系，以解决星形胶质细胞 AQP4 是否控制血脑界面的水交换。条件性敲除由神经胶质纤维酸性蛋白启动子驱动。通过 Western blot 评估，条件性 Aqp4 敲除小鼠的脑组织中缺乏 AQP4，排除了内皮细胞中存在大量 AQP4 的可能性。免疫荧光分析冷冻切片和超薄切片的定量免疫金分析均未显示毛细血管内皮中有 AQP4 信号。与同窝对照相比，胶质条件性 Aqp4 敲除小鼠在全身低渗应激后脑水摄取减少 31%，并且脑水的产后吸收延迟。星形胶质细胞 Aqp4 的缺失并不影响大分子的屏障功能。我们的数据表明血脑屏障（BBB）比预期的更为复杂。值得注意的是，在某些条件下，脑微血管上的星形胶质细胞覆盖物对水的运动起限速作用。
