Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Noradrenaline is essential for mouse fetal development

Abstract

CATECHOLAMINES such as noradrenaline and adrenaline have been implicated in numerous physiological processes1–4 but, although catecholamine synthesis begins at mid-gestation5, previous studies have provided little evidence for any role in early development6,7. Furthermore, there are several case reports of humans with noradrenaline deficiency8. To investigate this, we used gene targeting9 to produce mice lacking dopamine β-hydroxylase and therefore unable to synthesize noradrenaline or adrenaline. We report here that in heterozygous mothers, most homozygous embryos died in utero, and only about 5% reached adulthood. Survival probably depends on catecholamine transfer across the placenta because, in homozygous mothers, all embryos die in utero. Mortality was due to lack of noradrenaline in utero because it could be prevented by treatment with dihydroxyphenylserine, a precursor that can be converted to noradrenaline in the absence of dopamine β-hydroxylase. Mutant embryos had a histological phenotype similar to that of embryos deficient in tyrosine hydroxylase10, suggesting that death might be due to cardiovascular failure.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Cannon, W. B. & Rosenbluth, A. Autonomic Neuroeffector Systems (Macmillan, New York, 1937).

    Google Scholar 

  2. Levi-Montalcini, R. & Angeletti, P. U. Pharmac. Rev. 18, 619–628 (1966).

    CAS  Google Scholar 

  3. Berti, F., Lentati, R. & Usardi, M. M. Med. pharmac. Exp. 13, 227–232 (1965).

    CAS  Google Scholar 

  4. Angeletti, P. U. & Levi-Montalcini, R. Proc. natn. Acad. Sci. U.S.A. 65, 114–121 (1970).

    Article  ADS  CAS  Google Scholar 

  5. Schlumpf, M., Lichtensteiger, W., Shoemaker, W. J. & Bloom, F. E. in Biogenic Amines in Development (eds Parvez, H. & Parvez, S.) 567–590 (Elsevier North Holland Biomedical Press, Amsterdam, 1980).

    Google Scholar 

  6. Rosen, T. S., Lin, M., Spector, S. & Rosen, M. R. J. pharmac. exp. Ther. 208, 118–122 (1979).

    CAS  Google Scholar 

  7. Kudlacz, E. M., Navarro, H. A., Eylers, J. P. & Slotkin, T. A. J. dev. Physiol. 13, 243–249 (1990).

    CAS  PubMed  Google Scholar 

  8. Roberts, D. et al. Hypertension 18, 1–8 (1991).

    Article  Google Scholar 

  9. Cappechi, M. R. Science 244, 1288–1292 (1989).

    Article  ADS  Google Scholar 

  10. Zhou, Q.-Y., Quaife, C. J. & Palmiter, R. D. Nature 374, 640–643 (1995).

    Article  ADS  CAS  Google Scholar 

  11. Morgon, C. D., Sandier, M. & Panigel, M. Am. J. obstet. Gynecol. 112, 1068–1075 (1972).

    Article  Google Scholar 

  12. Parvez, S. & Parvez, H. Hormone Res. 5, 321–330 (1974).

    Article  CAS  Google Scholar 

  13. Kato, T., Karai, N., Katsuyama, M., Nakamura, M. & Katsube, J. Biochem. Pharmac. 36, 3051–3057 (1987).

    Article  CAS  Google Scholar 

  14. Jones, C. T. & Robinson, R. O. J. Physiol. 248, 15–33 (1975).

    Article  CAS  Google Scholar 

  15. Seidler, F. J. & Slotkin, T. A. J. Physiol. 358, 1–16 (1985).

    Article  CAS  Google Scholar 

  16. Baldessarini, R. J. J. Neurochem. 18, 2509–2518 (1971).

    Article  CAS  Google Scholar 

  17. David, J. C., Cavoy, A., Coulon, J. F. & Delacour, J. Neuroscience 12, 1271–1276 (1984).

    Article  CAS  Google Scholar 

  18. Theiler, K. The House Mouse: Atlas of Embryonic Development (Springer, New York, 1989).

    Book  Google Scholar 

  19. Liebmann, J. E. & Matsumoto, A. M. Endocrinology 126, 555 (1990).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thomas, S., Matsumoto, A. & Palmiter, R. Noradrenaline is essential for mouse fetal development. Nature 374, 643–646 (1995). https://doi.org/10.1038/374643a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/374643a0

This article is cited by

Comments

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.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing