The Vasopressin Type 2 Receptor Gene. Chromosomal Localization and Its Role in Nephrogenic Diabetes Insipidus

Title: The Vasopressin Type 2 Receptor Gene. Chromosomal Localization and Its Role in Nephrogenic Diabetes Insipidus
Authors: Rosenthal, Walter; Birnbaumer, Mariel; Seibold, Anita; Bichet, Daniel G.
Publisher: Regulatory Peptides
Date Published: April 29, 1993
Reference Number: 136

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)

Building on research that resulted with the cloning of the human vasopressin receptor (V2R), and using advanced methods for analyzing and mapping genes, Seibold, et al., set out to find if the gene that causes congenital nephrogenic diabetes insipidus (CNDI) was indeed the V2R gene. Their work confirmed that the V2R gene is located in the q28-qrtr portion of the X chromosome. The authors analyzed DNA from CNDI patients. Genes are extremely small, their constituent parts many and smaller yet, and the slightest rearrangement of any of those parts is a mutation. Since genes provide building information, a change in the information results in a change in the thing being built. For example, in the first family with a member having CDNI the authors examined, the CDNI patient's V2R genes had a mutation in a series of nucleotide bases within the gene called codon 246 because one of six consecutive chemical structures called guanosines was missing. The authors predicted this mutation would result in the patient's V2R genes being shorter than normal V2R genes and therefore incomplete because their growth would stop prematurely.

An unrelated CDNI patient had a different type of mutation of his V2R gene. In this patient, the amino acid Alanine that should have resulted from codon 132 was missing and in its place was the amino acid Aspartic acid. Other families in which members had CDNI had neither of these mutations, and the authors are currently mapping the structure of their mutations.

Next, the authors will study the mutated V2R genes they have identified in the families to see how these amino acid changes affect the receptor's ability to accept the message of the antidiuretic hormone, vasopressin. They will also examine their V2R to see if it can couple with a G protein called Gs as a normal V2R can. In addition, they also will study whether or not their improperly folded V2Rs can exit the part of the cell called the endoplasmic reticulum as this would affect the level that the V2R can express itself. The researchers expect there will be a great number of different mutations in the V2R gene that result in CDNI, and though final knowledge of the structure and function of the V2R gene is beyond the authors at present, progress is being made.