Aquaporin null phenotypes: The importance of classical physiology

The paper by Schnermann and colleagues (1) in this issue of the Proceedings is an excellent example of how the application of classical physiological measurements to tissues from transgenic mice successfully answered an important biological question: how is water reabsorbed by renal proximal tubules? The human kidney plays an important role in waste removal by filtering approximately 200 liters of plasma per day from which essential solutes are reabsorbed along with most of the water. Renal proximal tubules and descending thin limbs of Henle’s loop are the sites where approximately 80% of this fluid is reabsorbed. The vectorial distribution of salt and sugar transporters at the apical membranes (facing the urinary lumen) or basolateral membranes (facing the interstitium) together create a small-standing osmotic gradient across the tubular epithelium. Thus, the interstitium is slightly hyperosmolar with respect to …