Letter | Published:

Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus

Naturevolume 359pages233235 (1992) | Download Citation



ANTIDIURETIC hormone (arginine vasopressin) binds to and activates V2 receptors in renal collecting tubule cells. Subsequent stimulation of the Gs/adenylyl cyclase system promotes insertion of water pores into the luminal membrane and thereby reabsorption of fluid. In congenital nephrogenic diabetes insipidus (CNDI)1, an X-linked recessive disorder, the kidney fails to respond to arginine vasopressin. Here we report that an affected male of a family with CNDI2,3 has a deletion in the open reading frame of the V2 receptor gene, causing a frame shift and premature termination of translation in the third intracellular loop of the receptor protein. A normal receptor gene was found in the patient's brother. Both the normal and the mutant allele were detected in his mother. A different mutation, causing a codon change in the third transmem-brane domain of the V2 receptor, was found in the open reading frame of an affected male but not in the unaffected brother belonging to another family suffering from CNDI.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Reeves, W. B. & Andreoli, T. E. in The Metabolic Basis of Inherited Disease 6th edn (eds Scriver, C. R., Beaudet, A. L., Sly, W. S. & Valle, D.) 1985–2011 (McGraw-Hill, New York, 1989).

  2. 2

    Bichet, D. G. et al. New Engl. J. Med. 318, 881–887 (1988).

  3. 3

    Bichet, D. G. et al. Am. J. hum. Genet. (in the press).

  4. 4

    Seibold, A., Brabet, P., Rosenthal, W. & Birnbaumer, M. Am. J. hum. Genet. (in the press).

  5. 5

    Saiki, R. K. et al. Science 239, 487–491 (1988).

  6. 6

    Perez-Reyes, E., Wel, X., Castellano, A. & Birnbaumer, L. J. biol. Chem. 265, 20430–20436 (1990).

  7. 7

    Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

  8. 8

    Birnbaumer, M. et al. Nature 357, 333–335 (1992).

  9. 9

    Kobilka, B. K. et al. Science 240, 1310–1316 (1988).

  10. 10

    Sung, C.-H., Schneider, B. G., Agarwal, N., Papermaster, D. S. & Nathans, J. Proc. natn. Acad. Sci. U.S.A. 88, 8840–8844 (1991).

  11. 11

    Knoers, N. et al. Nephron 50, 187–190 (1988).

  12. 12

    Jans, D. A., van Oost, B. A., Ropers, H. H. & Fahrenholz, F. J. biol. Chem. 265, 15379–15382 (1990).

  13. 13

    Gyllenstein, U. B. & Ehrlich, H. Proc. natn. Acad. Sci. U.S.A. 85, 7652–7656 (1988).

  14. 14

    Kyte, J. & Doolittle, R. F. J. molec. Biol. 157, 105–132 (1982).

  15. 15

    Bichet, D. G. et al. Kidney Int. 36, 859–866 (1989).

  16. 16

    Moses, A. M. & Coulson, B. B. J. clin. Endocr. Metab. 55, 699–702 (1982).

  17. 17

    Patten, J. L. et al. New Engl. J. Med. 322, 1412–1419 (1988).

  18. 18

    DiLella, A. G. & Woo, S. L. C. Meth. Enzym. 152, 199–212 (1987).

  19. 19

    Hanahan, D. in DNA Cloning (ed. Glover, D. M.) 109–135 (IRL, Oxford, 1985).

  20. 20

    Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning (Cold Spring Harbor Laboratory Press, New York 1989).

  21. 21

    Gibbs, R. A., Nguyen, P.-N. & Caskey, C. T. in Methods in Molecular Biology Vol. 8 (ed. Mathew, C.) 9–20 (Human Press, Clifton, New York, 1991).

  22. 22

    Karnik, S. S., Sakmar, T. P., Chen, H.-B. & Khorana, H. G. Biochemistry 85, 8459–8463 (1988).

Download references

Author information


  1. Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA

    • Walter Rosenthal
    • , Anita Seibold
    • , Anaid Antaramian
    •  & Mariel Birnbaumer
  2. Service de Néphrologie, Centre de Recherche, Hôpital du Sacre-Coeur de Montréal et Département de Médecine, Université de Montréal, Montréal, Québec, H4J 1C5, Canada

    • Michèle Lonergan
    • , Marie-Francoise Arthus
    • , Geoffrey N. Hendy
    •  & Daniel G. Bichet


  1. Search for Walter Rosenthal in:

  2. Search for Anita Seibold in:

  3. Search for Anaid Antaramian in:

  4. Search for Michèle Lonergan in:

  5. Search for Marie-Francoise Arthus in:

  6. Search for Geoffrey N. Hendy in:

  7. Search for Mariel Birnbaumer in:

  8. Search for Daniel G. Bichet in:

About this article

Publication history



Issue Date



Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.