水通道蛋白的生理功能 ——水通道基因敲除小鼠表型研究进展

水通道蛋白 (aquaporin， AQP) 是一族细胞膜上选择性高效转运水分子的特异孔道. 自从 Agre 等于 1992 年从红细胞膜发现第一个水通道蛋白 AQP1以来，有关水通道蛋白结构与功能的研究取得了迅速的、系列性的进展 . 已报道的哺乳动物 AQP 家族已有 11 个在蛋白质序列上有同源性成员 (AQP0~AQP10). AQP 在体内各系统组织中广泛表达，除了在与体液分泌和吸收密切相关的多种上皮和内皮细胞高表达外，在一些与体液转运无明显关系的组织细胞如红细胞、白细胞、脂肪细胞和骨骼肌细胞等处也有表达，提示 AQP 可能在多种器官生理和病理中发挥重要作用. 基因打靶技术是研究特定基因在体内生理功能的有力手段. 目前 AQP1、3、4、5 基因敲除和 AQP2 基因点突变的基因敲入小鼠模型 ( 模拟人类常染色体隐性遗传尿崩症 ) 已成功建立并广泛用于表型研究，在 AQP 水通道蛋白生理功能方面获得许多重要进展.

Physiological Importance of Aquaporin Water Channels Accessed by Phenotype Studies of Aquaporin Knockout Mice

Aquaporins (AQP) are a family of hydrophobic intrinsic membrane proteins that efficiently and selectively transport water. Since the discovery of first water channel (AQP1) from red blood cell membrane by Agre et al in 1992, rapid and serial progresses have been made in characterization of AQP structure and function. At least 11 homologous members (AQP0 - AQP10) have been molecularly identified in mammals. AQPs are expressed in various epithelium and endothelium involving fluid secretion and absorption, and in many cell types such as erythrocytes, white blood cells, adipocytes, and muscle fibers that have no obvious relationship with fluid transport. The extensive expression pattern of AQPs may indicate functional importance in multiorgan physiology and pathophysiology. Gene-targeting technology has been a powerful tool in defining physiological functions of specific genes. So far transgenic knockout models of AQP1, AQP3, AQP4 and AQP5, and a knock-in model introducing a point mutation (T126M) that causes autosomal recessive nephrogenic diabetes insipidus (NDI) in human have been successfully established. Significant progresses have been made in characterizing the physiological functions of these AQPs by systematic mouse phenotype studies.