Lu Daniel C, Zhang Hua, Zador Zsolt, Verkman A S
Department of Medicine, University of California, San Francisco, CA 94143, USA.
FASEB J. 2008 Sep;22(9):3216-23. doi: 10.1096/fj.07-104836. Epub 2008 May 29.
Aquaporin-4 (AQP4) is a water-selective transport protein expressed in glial cells throughout the central nervous system. AQP4 deletion in mice produces alterations in several neuroexcitation phenomena, including hearing, vision, epilepsy, and cortical spreading depression. Here, we report defective olfaction and electroolfactogram responses in AQP4-null mice. Immunofluorescence indicated strong AQP4 expression in supportive cells of the nasal olfactory epithelium. The olfactory epithelium in AQP4-null mice had identical appearance, but did not express AQP4, and had approximately 12-fold reduced osmotic water permeability. Behavioral analysis showed greatly impaired olfaction in AQP4-null mice, with latency times of 17 +/- 0.7 vs. 55 +/- 5 s in wild-type vs. AQP4-null mice in a buried food pellet test, which was confirmed using an olfactory maze test. Electroolfactogram voltage responses to multiple odorants were reduced in AQP4-null mice, with maximal responses to triethylamine of 0.80 +/- 0.07 vs. 0.28 +/- 0.03 mV. Similar olfaction and electroolfactogram defects were found in outbred (CD1) and inbred (C57/bl6) mouse genetic backgrounds. Our results establish AQP4 as a novel determinant of olfaction, the deficiency of which probably impairs extracellular space K(+) buffering in the olfactory epithelium.
水通道蛋白4（AQP4）是一种在整个中枢神经系统的神经胶质细胞中表达的水选择性转运蛋白。小鼠中AQP4的缺失会导致几种神经兴奋现象发生改变，包括听力、视力、癫痫和皮层扩散性抑制。在此，我们报告了AQP4基因敲除小鼠存在嗅觉缺陷和嗅觉电图反应异常。免疫荧光显示鼻嗅上皮的支持细胞中有强烈的AQP4表达。AQP4基因敲除小鼠的嗅上皮外观相同，但不表达AQP4，其渗透水通透性降低了约12倍。行为分析表明，AQP4基因敲除小鼠的嗅觉严重受损，在掩埋食物颗粒试验中野生型小鼠与AQP4基因敲除小鼠的潜伏期分别为55±5秒和17±0.7秒，嗅觉迷宫试验也证实了这一点。AQP4基因敲除小鼠对多种气味剂的嗅觉电图电压反应降低，对三乙胺的最大反应为0.28±0.03毫伏，而野生型为0.80±0.07毫伏。在远交（CD1）和近交（C57/bl6）小鼠遗传背景中也发现了类似的嗅觉和嗅觉电图缺陷。我们的研究结果确定AQP4是嗅觉的一个新的决定因素，其缺乏可能会损害嗅上皮细胞外空间的钾离子缓冲功能。
