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- Title
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.
- Authors
Nejsum, Lene N.; Christensen, Tomas M.; Robben, Joris H.; Milligan, Graeme; Deen, Peter M. T.; Bichet, Daniel G.; Levin, Klaus
- 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.
- Subjects
VASOTOCIN; GENETIC mutation; GENES; HORMONES; CELL culture
- Publication
NDT Plus, 2011, Vol 4, Issue 3, p158
- ISSN
1753-0784
- Publication type
Article
- DOI
10.1093/ndtplus/sfr010