Aquaporin water channels in mammals.

Water channels, aquaporins (AQPs), are a family of small integral plasma membrane proteins that primarily transport water across the plasma membrane. There are 13 members (AQP0-12) in humans. This number is final as the human genome project has been completed. They are divided into three subgroups based on the primary sequences: water selective AQPs (AQP0, 1, 2, 4, 5, 6, 8), aquaglyceroporins (AQP3, 7, 9, 10), and superaquaporins (AQP11, 12). Since no specific inhibitors are yet available, functional roles of AQPs are suggested by AQP null mice and humans. Abnormal water metabolism was shown with AQP1, 2, 3, 4, 5 null mice, especially with AQP2 null mice: fatal at neonate due to diabetes insipidus. Abnormal glycerol transport was shown with AQP3, 7, 9 null mice, although they appeared normal. AQP0 null mice suffer from cataracts, although the pathogenesis is not clear. Unexpectedly, AQP11 null mice die from uremia as a result of polycystic kidneys. Interestingly, AQP6, 8, 10, 12 null mice are almost normal. AQP null humans have been reported with AQP0, 1, 2, 3, 7: only AQP2 null humans show an outstanding phenotype, diabetes insipidus. This review summarizes the current knowledge on all mammalian AQPs and hopefully will stimulate future research in both clinical and basic fields.