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Molecular genetic study of congenital nephrogenic diabetes insipidus and rescue of mutant vasopressin V2 receptor by chemical chaperones

Cited 10 time in Web of Science Cited 12 time in Scopus
Authors
Cheong, Hae Il; Cho, Hee Yeon; Park, Hye Won; Ha, Il Soo; Choi, Yong
Issue Date
2007-03-21
Publisher
Wiley-Blackwell
Citation
Nephrology (Carlton). 2007 Apr;12(2):113-7.
Keywords
AnimalsArginine Vasopressin/genetics/*metabolismCOS CellsCell Membrane/metabolismCercopithecus aethiopsDiabetes Insipidus, Nephrogenic/genetics/*metabolismDimethyl Sulfoxide/*pharmacologyHumansMaleMethylamines/*pharmacologyMolecular Chaperones/pharmacology*MutationMutation, MissensePoint MutationProtein FoldingProtein Transport/drug effectsReceptors, Vasopressin/chemistry/genetics/*metabolismTemperatureTransfection
Abstract
AIM: X-linked nephrogenic diabetes insipidus is a rare disease caused by mutations in the arginine vasopressin V2 receptor (AVPR2) gene, which encodes vasopressin V2 receptor (V2R). More than a half of reported mutations in AVPR2 are missense mutations, and a large number of missense mutant receptors fail to fold properly and therefore are not routed to the cell surface. METHODS: We analysed the AVPR2 gene in 14 unrelated patients with X-linked nephrogenic diabetes insipidus, and found 13 different mutations including eight missense point mutations. The cellular expression patterns of three missense mutant (A98P, L274P and R113W) and wild-type V2R were determined in transfected COS-7 cells. RESULTS: In contrast to wild-type V2R, the cell-surface expressions of mutant receptors were totally (A98P and L274P) or partially (R113W) absent. Instead, they were retained intracellularly. However, treatment of cells with two chemical chaperones (100 mmol/L trimethylamine oxide or 2% dimethyl sulfoxide) or incubation at 26 degrees C restored the cell-surface expressions of mutant receptors. CONCLUSION: These data show that some chemical chaperones correct the mistrafficking of misfolded A98P, L274P and R113W V2R. Thus, we believe that a therapeutic strategy based on chemical chaperones in patients with these mutations is worth trying.
ISSN
1320-5358 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17371330

http://hdl.handle.net/10371/46584
DOI
https://doi.org/10.1111/j.1440-1797.2006.00759.x
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College of Medicine/School of Medicine (의과대학/대학원)Molecular and Genomic Medicine (분자유전체의학전공)Journal Papers (저널논문_분자유전체의학전공)
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