Journal Article

Identification and Characterization of Aquaporin-2 Water Channel Mutations Causing Nephrogenic Diabetes Insipidus with Partial Vasopressin Response

Marie C. Canfield, B. K. Tamarappoo, Arnold M. Moses, A. S. Verkman and Eli J. Holtzman

in Human Molecular Genetics

Volume 6, issue 11, pages 1865-1871
Published in print October 1997 | ISSN: 0964-6906
Published online October 1997 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/6.11.1865
Identification and Characterization of Aquaporin-2 Water Channel Mutations Causing Nephrogenic Diabetes Insipidus with Partial Vasopressin Response

Show Summary Details

Preview

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 l/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aqua-porins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to ∼60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.

Journal Article.  4141 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.