2000 Global Researcher Conference Proceeding
March 10 - 12, 2000
|Conference:||2000 Global Researcher Conference|
|Title:||Nephrogenic Diabetes Insipidus in mice lacking aquaporin-3 water channels|
|Authors:||Ma, Tonghui; Song, M.D., Yuanlin; Yang, Baoxue; Gillespie, Annemarie; Carlson, Elaine J.; Epstein, Charles; Verkman, Alan S.|
|Institutions:||University of California, S.F., University of California, San Francisco, University of California|
Aquaporins (AQPs) are a family of proteins that allow water to transport across cell membranes. One result of mutations in aquaporin-2 (AQP2) genes is nephrogenic diabetes insipidus (NDI), a condition wherein the kidneys are unable to concentrate urine. NDI patients exhibit polyuria (excessive urination) and polydipsia (excessive thrist). Ma, et al., generated a line of mice lacking AQP3. These mice exhibited polyuria, polydipsia and dilute urine. They also had fewer AQP2s than normal mice. They responded to injections of DDAVP, a modified form of the antidiuretic hormone, arginine vasopressin (AVP), by showing a slight increase in their ability to concentrate urine. When Ma, et al., generated a line of mice lacking both AQP3 and AQP4, the mice had an even greater inability to concentrate their urine. Whereas AQP2 functions at the top of the membrane of kidney collecting duct principal cells (i.e. the apical membrane), AQP3 operates at the base and sides of the principal cell membrane (i.e. the basolateral membrane).
The researchers, then, have found that a form of NDI is produced when the basolateral membrane’s ability to transport water is impaired. Focusing on basolateral membrane AQPs may provide blood-accessible avenues for drugs that may help treat NDI.