Functional Characterization of Five V2 Vasopressin Receptor Gene Mutations
| Title: | Functional Characterization of Five V2 Vasopressin Receptor Gene Mutations |
|---|---|
| Authors: | Wenkert, M.D., Ph.D., David; Schoneberg, Torsten; Merendino, Jr., John J.; Pena, Maria Sol Rodriguez; Vinitsky, MD, Ruth; Goldsmith, Paul K.; Wess, Jurgen; Spiegel, M.D., Allen M. |
| Publisher: | Molecular and Cellular Endocrinology |
| Date Published: | November 29, 1996 |
| Reference Number: | 6 |
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)
X-linked nephrogenic diabetes insipidus (NDI) is a rare disease in which the kidneys do not respond to the anti-diuretic hormone (ADH). This hormone tells the kidneys that the blood needs to be diluted. To do this, the kidneys retain water rather than passing it into urine. When the kidneys don't respond to ADH, they pass water into urine. Researchers have shown that this disease is caused by mutations in the V2 vasopressin receptor gene. We recently identified several new mutations in this gene: G12E, L292P, Y280C, R337stop, and the V277A. This study describes the expression and functional effects of these mutations.
Discussion
X-Linked NDI is caused when the mutations in the V2 vasopressin receptors on the X chromosome do not do what they are supposed to do. In this study, we examined functional consequences of five V2 vasopressin receptor mutations found in four unrelated people with NDI. Functional analysis of the G12E mutant showed no significant difference from the normal receptor in either binding or cAMP stimulation, i.e., the receptor was able to do what it was supposed to do. Therefore, the G12E mutation probably did not cause NDI in the person; it has also been identified in people who were not known to have relatives with NDI. Three other mutations, the L292P, Y280C, and R337stop, are null mutations; they failed to show specific binding or agonist-stimulated cAMP production, i.e., they were not able to do their jobs. Therefore, these mutations probably cause complete vasopressin resistance in people; the kidneys do not know that they must retain water to thin out the blood. The V277A mutation did not completely abolish specific AVP binding and stimulation of cAMP, though the binding and stimulation were significantly reduced compared with normal receptors. In other words, this receptor could do what it's supposed to do; it just couldn't do it very well. The AVP levels would have to be quite high in order for this receptor to tell the kidneys to retain water to thin out the blood.