Requirement of Human Renal Water Channel Aquaporin-2 for Vasopressin-Dependent Concentration of Urine
| Title: | Requirement of Human Renal Water Channel Aquaporin-2 for Vasopressin-Dependent Concentration of Urine |
|---|---|
| Authors: | Deen, Peter M.T.; Verdijk, Marian A.J.; Knoers, Nine; Wieringa, Be; Monnens, Leo A.H.; van Os, Carel; van Oost, Bernard A. |
| Publisher: | Science |
| Date Published: | April 01, 1994 |
| Reference Number: | 106 |
Concentration of urine in mammals is regulated by the antidiuretic hormone vasopressin. Binding of vasopressin to its V2 receptor leads to the insertion of water channels in apical membranes of principal cells in collecting ducts. In nephrogenic diabetes insipidus (NDI), the kidney fails to concentrate urine in response to vasopressin. A male patient with an autosomal recessive form of NDI was found to be a compound heterozygote for two mutations in the gene encoding aquaporin-2, a water channel. Functional expression studies in Xenopus oocytes revealed that each mutation resulted in nonfunctional water channel proteins. Thus, aquaporin-2 is essential for vasopressin-dependent concentration of urine.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
Nephrogenic diabetes insipidus (NDI) is a disorder marked by the kidneys' inability to reabsorb water and concentrate urine. The most common form of inherited NDI is X-linked NDI. This involves mutations of the V2R gene that produce V2Rs incapable of binding with AVP. And if the binding does not take place, the molecular sequence which inserts AQP2 in the membrane of the kidney duct's principal cells does not occur.
Deen, et al., studied a male NDI patient with an autosomal recessive form of inheritance and no mutations of the V2R gene. Since AQP2's are also vital to the urine concentrating process, the authors checked for mutations in their patient's AQP2 gene. Genes come in pairs and the authors found that both of the patient's AQP2 genes had mutations, one inherited from his mother and one from his father.
The AQP2 genes produce AQP2s, which are proteins made up of amino acids. The structure of the protein is determined by the sequence of the amino acids. The type of AQP2 gene mutations the boy had caused the replacement of the amino acid normally present at one point in the amino acid sequence with another amino acid. This alters the structure of the AQP2.
The authors tested to see if the altered structure changed the ability of the AQP2s to function. They cloned the two mutant AQP2 genes and let them produce their respective AQP2s. They then injected laboratory cell cultures with the altered AQP2s and found they did not increase the water permeability of the cell's membranes. Thus the mutant AQP2 genes produced non-functional AQP2s. This showed both that mutant AQP2 genes are one cause of NDI, and that AQP2 is the AVP regulated water-transporting protein in humans.