| Mutations in the vasopressin V2 receptor gene in families with nephrogenic diabetes insipidus and functional expression of the Q-2 mutant. | |
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MedLine Citation:
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PMID: 7920187 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nephrogenic diabetes insipidus (NDI) is characterized by a resistance of the kidney towards arginine vasopressin (AVP). Following molecular cloning of the vasopressin V2 receptor, we identified different mutations in the V2 receptor gene in families with X-linked NDI, which segregated with the disease. The Hopewell mutation (W71X) causes the disease in the largest North American NDI pedigree, with most of its members residing on Nova Scotia. Different mutations were found in three families from the Quebec area (Q-2: R137H, Q-3: R113W, Q-5: 804delG) and in the large Cannon kindred residing in Utah (L312X). In an Iranian family (O-1), another mutation was detected (A132D). Three of the six mutations (Hopewell, Cannon, Q-5) are predicted to cause the expression of a truncated V2 receptor and are therefore unlikely to function. The functional consequences of missense mutations (Q-2, Q-3, O-1) are less obvious. We therefore introduced the Q-2 mutation into wild-type cDNA. When expressed in COS.M6 or Ltk cells, the Q-2 mutant bound AVP with normal affinity. However, cells expressing the Q-2 mutant failed to respond to AVP with an increase in adenylyl cyclase activity. Thus the Q-2 mutant is unable to interact with or to activate the stimulatory G-protein Gs. The present data indicate that X-linked NDI is frequently attributable to a mutation in the V2 receptor gene. In addition, the data prove biochemically that the Q-2 mutation is the cause of NDI in the Q-2 family. |
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Authors:
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W Rosenthal; A Seibold; A Antaramian; S Gilbert; M Birnbaumer; D G Bichet; M F Arthus; M Lonergan |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cellular and molecular biology (Noisy-le-Grand, France) Volume: 40 ISSN: 0145-5680 ISO Abbreviation: Cell. Mol. Biol. (Noisy-le-grand) Publication Date: 1994 May |
Date Detail:
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Created Date: 1994-10-26 Completed Date: 1994-10-26 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 9216789 Medline TA: Cell Mol Biol (Noisy-le-grand) Country: FRANCE |
Other Details:
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Languages: eng Pagination: 429-36 Citation Subset: IM |
Affiliation:
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Baylor College of Medicine, Department of Cell Biology, Houston, Texas 77030. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence DNA Mutational Analysis Diabetes Insipidus / classification, epidemiology, ethnology, genetics* Gene Frequency Humans Molecular Sequence Data Mutation* North America / epidemiology Point Mutation Prevalence Protein Conformation Receptors, Vasopressin / biosynthesis, genetics* Sequence Deletion X Chromosome |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Vasopressin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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