Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene

June Yun, Torsten Schöneberg, Jie Liu, Angela Schulz, Carolyn A. Ecelbarger, Dominique Promeneur, Soren Nielsen, Hui Sheng, Alexander Grinberg, Chu Xia Deng, Jürgen Wess

Research output: Contribution to journalArticle

Abstract

The V2 vasopressin receptor (V2R) plays a key role in the maintenance of a normal body water balance. To generate an in vivo model that allows the physiological and molecular analysis of the role of V2Rs in kidney function, we have created mouse lines that lack functional V2Rs by using targeted mutagenesis in mouse embryonic stem cells. Specifically, we introduced a nonsense mutation known to cause X-linked nephrogenic diabetes insipidus (XNDI) in humans (Glu242stop) into the mouse genome. V2R-deficient hemizygous male pups showed a decrease in basal urine osmolalities and were unable to concentrate their urine. These pups also exhibited an enlargement of renal pelvic space, failed to thrive, and died within the first week after birth due to hypernatremic dehydration. Interestingly, female mice heterozygous for the V2R mutation showed normal growth but displayed an XNDI-like phenotype, characterized by reduced urine concentrating ability of the kidney, polyuria, and polydipsia. Western blot analysis and immunoelectron microscopic studies showed that the loss of functional V2Rs had no significant effect on the basal expression levels of aquaporin-2 and the bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1). The V2R mutant mice described here should serve as highly useful tools for the development of novel therapeutic strategies for the treatment of XNDI.

Original languageEnglish (US)
Pages (from-to)1361-1371
Number of pages11
JournalJournal of Clinical Investigation
Volume106
Issue number11
StatePublished - 2000
Externally publishedYes

Fingerprint

Vasopressin Receptors
Nonsense Codon
Nephrogenic Diabetes Insipidus
Phenotype
Kidney
Genes
Kidney Concentrating Ability
Aquaporin 2
Urine
Polydipsia
Bumetanide
Polyuria
Body Water
Dehydration
Mutagenesis
Osmolar Concentration
Western Blotting
Maintenance
Parturition
Genome

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yun, J., Schöneberg, T., Liu, J., Schulz, A., Ecelbarger, C. A., Promeneur, D., ... Wess, J. (2000). Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene. Journal of Clinical Investigation, 106(11), 1361-1371.

Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene. / Yun, June; Schöneberg, Torsten; Liu, Jie; Schulz, Angela; Ecelbarger, Carolyn A.; Promeneur, Dominique; Nielsen, Soren; Sheng, Hui; Grinberg, Alexander; Deng, Chu Xia; Wess, Jürgen.

In: Journal of Clinical Investigation, Vol. 106, No. 11, 2000, p. 1361-1371.

Research output: Contribution to journalArticle

Yun, J, Schöneberg, T, Liu, J, Schulz, A, Ecelbarger, CA, Promeneur, D, Nielsen, S, Sheng, H, Grinberg, A, Deng, CX & Wess, J 2000, 'Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene', Journal of Clinical Investigation, vol. 106, no. 11, pp. 1361-1371.
Yun J, Schöneberg T, Liu J, Schulz A, Ecelbarger CA, Promeneur D et al. Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene. Journal of Clinical Investigation. 2000;106(11):1361-1371.
Yun, June ; Schöneberg, Torsten ; Liu, Jie ; Schulz, Angela ; Ecelbarger, Carolyn A. ; Promeneur, Dominique ; Nielsen, Soren ; Sheng, Hui ; Grinberg, Alexander ; Deng, Chu Xia ; Wess, Jürgen. / Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene. In: Journal of Clinical Investigation. 2000 ; Vol. 106, No. 11. pp. 1361-1371.
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