A LOW-AFFINITY VASOPRESSIN V2-RECEPTOR GENE IN A KINDRED WITH X-LINKED NEPHROGENIC DIABETES-INSIPIDUS

In this study, a mutation in vasopressin Type 2 receptor (V2R) in a pa tient with hereditary nephrogenic diabetes insipidus (NDI) has been id entified and characterized, The sequencing of the V2R gene from the pa tient revealed that there was a missense mutation (TAT to TGT) resulti ng in the substitution of (205)Tyr for Cys in the putative third extra cellular domain. The expression analysis in COS cells showed that the binding affinity of the mutant receptor (K-D = 19.8 nM) for arginine v asopressin was much lower than that of the wild-type receptor (K-D = 1 .8 nM) so that intracellular cAMP production stimulated by arginine va sopressin was impaired in cells with the mutant V2R. From these result s, it was concluded that the single amino-acid substitution of V2R is responsible for this familial disease.