Novel mutation in the AVPR2 gene in a Danish male with nephrogenic diabetes insipidus caused by ER retention and subsequent lysosomal degradation of the mutant receptor

Nejsum, L.N., Christensen, T.M., Robben, J.H., Milligan, G. , Deen, P.M.T., Bichet, D.G. and Levin, K. (2011) Novel mutation in the AVPR2 gene in a Danish male with nephrogenic diabetes insipidus caused by ER retention and subsequent lysosomal degradation of the mutant receptor. NDT Plus, 4(3), pp. 158-163. (doi: 10.1093/ndtplus/sfr010) (PMID:21629670) (PMCID:PMC3103721)

Abstract

Mutations in the arginine vasopressin receptor 2 (AVPR2) gene can cause X-linked nephrogenic diabetes insipidus (NDI) characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel mutation in the AVPR2 gene (L170P) located in the fourth transmembrane domain in a Danish NDI male. Analysis of the mutant receptor in Madin-Darby Canine Kidney cell culture revealed that AVPR2-L170P was retained in the endoplasmic reticulum, and the expression was dramatically downregulated compared to wild-type AVPR2. Inhibition of the lysosome resulted in increased intracellular accumulation of AVPR2-L170P, indicating that AVPR2-L170P is downregulated via the lysosome. Inhibition of the proteasome resulted in plasma membrane localization of AVPR2-L170P, although the overall levels of AVPR2-L170P were unchanged.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Milligan, Professor Graeme
• Authors: Nejsum, L.N., Christensen, T.M., Robben, J.H., Milligan, G., Deen, P.M.T., Bichet, D.G., and Levin, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: NDT Plus
• Publisher: Oxford University Press
• ISSN: 1753-0784
• ISSN (Online): 1753-0792
• Published Online: 02 March 2011