Urea Transporter Physiology Studied in Knockout Mice

In mammals, there are two types of urea transporters; urea transporter (UT)-A and UT-B. The UT-A transporters are mainly expressed in kidney epithelial cells while UT-B demonstrates a broader distribution in kidney, heart, brain, testis, urinary tract, and other tissues. Over the past few years, multiple urea transporter knockout mouse models have been generated enabling us to explore the physiological roles of the different urea transporters. In the kidney, deletion of UT-A1/UT-A3 results in polyuria and a severe urine concentrating defect, indicating that intrarenal recycling of urea plays a crucial role in the overall capacity to concentrate urine. Since UT-B has a wide tissue distribution, multiple phenotypic abnormalities have been found in UT-B null mice, such as defective urine concentration, exacerbated heart blockage with aging, depression-like behavior, and earlier male sexual maturation. This review summarizes the new insights of urea transporter functions in different organs, gleaned from studies of urea transporter knockout mice, and explores some of the potential pharmacological prospects of urea transporters.