Impaired hearing in mice lacking aquaporin-4 water channels
Impaired hearing in mice lacking aquaporin-4 water channels
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DOI：
10.1074/jbc.m104368200
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发表时间：
2001-08-17
影响因子：
4.8
通讯作者：
Verkman, AS
中科院分区：
文献类型：
--
作者：
Li, J;Verkman, AS
水通道蛋白 (AQP) 在内耳中的特异性表达以及参与声信号转导的上皮细胞精确音量调节的需要表明了水通道蛋白 (AQP) 在听力中的作用。使用缺乏选定水通道蛋白的小鼠作为对照，我们将 AQP1 定位于螺旋韧带的纤维细胞中，将 AQP4 定位于柯蒂氏器中支持上皮细胞（Hensen 细胞、Claudius 细胞和内沟细胞）中。为了确定水通道蛋白是否在听力中发挥作用，我们比较了野生型小鼠和（单独）缺乏 AQP1、AQP3、AQP4 和 AQP5 的转基因无效小鼠的听觉脑干反应 (ABR) 阈值。在 CD1 遗传背景的 4-5 周龄小鼠中，与野生型小鼠相比，AQP4 缺失小鼠响应点击刺激的 ABR 阈值显着增加 > 12 db (p < 0.001)，而 ABR 阈值不受 AQP1、AQP3 或 AQP5 缺失的影响。在 C57/b16 背景中，几乎所有 AQP4 缺失小鼠都是聋的，而在野生型对照中可以引发 ABR。在 AQP4 null CD1 小鼠中测量对突发音调 (4-20 kHz) 的 ABR 表明存在与频率无关的听力缺陷。光学显微镜显示野生型小鼠与 AQP4 缺失小鼠的耳蜗形态没有差异。这些结果首次提供了水通道蛋白水通道在听力中发挥作用的直接证据。 AQP4 可能促进柯蒂氏器上皮细胞的快速渗透平衡，这些细胞在机电信号转导过程中受到大量 K+ 通量的影响。
A role for aquaporins (AQPs) in hearing has been suggested from the specific expression of aquaporins in inner ear and the need for precise volume regulation in epithelial cells involved in acoustic signal transduction. Using mice deficient in selected aquaporins as controls, we localized AQP1 in fibrocytes in the spiral ligament and AQP4 in supporting epithelial cells (Hensen's, Claudius, and inner sulcus cells) in the organ of Corti. To determine whether aquaporins play a role in hearing, auditory brain stem response (ABR) thresholds were compared in wild-type mice and transgenic null mice lacking (individually) AQP1, AQP3, AQP4, and AQP5. In 4-5-week-old mice in a CD1 genetic background, ABR thresholds in response to a click stimulus were remarkably increased by > 12 db in AQP4 null mice compared with wild-type mice (p < 0.001), whereas ABR thresholds were not affected by AQP1, AQP3, or AQP5 deletion. In a C57/b16 background, nearly all AQP4 null mice were deaf, whereas ABRs could be elicited in wildtype controls. ABRs in AQP4 null CD1 mice measured in response to tone bursts (4-20 kHz) indicated a frequency-independent hearing deficit. Light microscopy showed no differences in cochlear morphology of wildtype versus AQP4 null mice. These results provide the first direct evidence that an aquaporin water channel plays a role in hearing. AQP4 may facilitate rapid osmotic equilibration in epithelial cells in the organ of Corti, which are subject to large K+ fluxes during mechano-electric signal transduction.