Aminoglycoside Pretreatment Partially Restores the Function of Truncated V2 Vasopressin Receptors Found in Patients with Nephrogenic Diabetes Insipidus
By screening patients with X-linked nephrogenic diabetes in- sipidus (NDI) for mutations within the V2 vasopressin recep- tor (AVPR2) gene, we have identified six novel and two re- current mutations. Additionally, one patient revealed a genomic deletion of 3.2 kb encompassing most of the AVPR2 gene and the last exon/3-region of C1 gene, which is in close proximity to the AVPR2 locus. In-depth characterization of the mutant AVPR2s by a combination of functional and im- munological techniques allowed to gain further insight into molecular mechanisms leading to the receptor dysfunction. Aiming at the functional reconstitution of mutant G protein- coupled receptors, several strategies of potential therapeutic usefulness have been tested. Because the functional rescue of truncated receptors is most challenging, we addressed this issue by applying an aminoglycoside approach. Here, we dem- onstrate that the misreading capacity of the aminoglycoside antibiotic geneticin was sufficient to restore function of mu- tant AVPR2s harboring premature stop codons in an in vitro expression system. (J Clin Endocrinol Metab 87: 5247-5257, 2002)
Published in 2010.