Physiological importance of aquaporins: lessons from knockout mice

The phenotype analysis of transgenic mice deficient in specific aquaporin w ater channels has provided new insights into the role of aquaporins in orga n physiology. AQP1-deficient mice are polyuric and are unable to concentrat e their urine in response to water deprivation or vasopressin administratio n, AQP1 deletion reduces osmotic water permeability in the proximal tubule, thin descending limb of Henle and vasa recta, resulting in defective proxi mal tubule fluid absorption and medullary countercurrent exchange. Mice lac king AQP3, a basolateral membrane water channel expressed mainly in the cor tical collecting duct, are remarkably polyuric but are able to generate a p artly concentrated urine after water deprivation. In contrast, mice lacking AQP4, a water channel expressed mainly in the inner medullary collecting d uct, manifest only a mild defect in maximum urinary concentrating ability, These data, together with phenotype analyses of the brain, lung, salivary g land, and gastrointestinal organs, support the paradigm that aquaporins can facilitate near-isosmolar transepithelial fluid absorption/secretion as we ll as rapid vectorial water movement driven by osmotic gradients. The pheno type data obtained from aquaporin knockout mice suggest the utility of aqua porin blockers as novel diuretic agents, Curr Opin Nephrol Hypertens 9:517- 522. (C) 2000 Lippincott Williams & Wilkins.