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:

Renal agenesis and the absence of enteric neurons in mice lacking GDNF

Abstract

GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF)1 is a potent survival factor for dopaminergic neurons and motor neurons in culture1,2. It also protects these neurons from degeneration in vitro3–9, and improves symptoms like Parkinson's disease induced pharmacologically in rodents10 and monkeys11. Thus GDNF might have beneficial effects in the treatment of Parkinson's disease and amyotrophic lateral sclerosis. To examine the physiological role of GDNF in the development of the mammalian nervous system, we have generated mice defective in GDNF expression by using homologous recombination in embryonic stem cells to delete each of its two coding exons1. GDNF-null mice, regardless of their targeted mutation, display complete renal agenesis owing to lack of induction of the ureteric bud, an early step in kidney development. These mice also have no enteric neurons, which probably explains the observed pyloric stenosis and dilation of their duodenum. However, ablation of the GDNF gene does not affect the differentiation and survival of dopaminergic neurons, at least during embryonic development.

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. Lin, L. F. H. et al. Science 260, 1130–1132 (1993).

    Article  ADS  CAS  Google Scholar 

  2. Henderson, C. E. et al. Science 226, 1062–1064 (1994).

    Article  ADS  Google Scholar 

  3. Zurn, A. D. et al. NeuroReport. 6 (1), 113–118 (1994).

    Article  CAS  Google Scholar 

  4. Beck, K. D. et al. Nature 373, 339–341 (1995).

    Article  ADS  CAS  Google Scholar 

  5. Kearns, C. M. & Gash, D. M. Brain Res. 672, 104–111 (1995).

    Article  CAS  Google Scholar 

  6. Li, L. X. et al. Proc. natn. Acad. Sci. U.S.A. 92, 9771–9775 (1995).

    Article  ADS  CAS  Google Scholar 

  7. Oppenheim, R. W. et al. Nature 373, 344–346 (1995).

    Article  ADS  CAS  Google Scholar 

  8. Tomac, A. et al. Nature 373, 335–339 (1995).

    Article  ADS  CAS  Google Scholar 

  9. Yan, Q., Matheson, C. & Lopez, O. T. Nature 373, 341–344 (1995).

    Article  ADS  CAS  Google Scholar 

  10. Hoffer, B. J. et al. Neurosci. Lett. 182 (1), 107–111 (1994).

    Article  CAS  Google Scholar 

  11. Gash, M. D. et al. Nature 380, 252–255 (1966).

    Article  ADS  Google Scholar 

  12. Hellmich, H. L. et al. Mech. Dev. 54, 95–105 (1996).

    Article  CAS  Google Scholar 

  13. Saxen, L. Oiganogenesis of the Kidney Vol. 19 (eds Barlow, P. W., Green, P. B., and Wylie, C. C.) (Cambridge Univ. Press, 1987).

    Book  Google Scholar 

  14. Blaugrund, E. et al. Development 122, 309–320 (1996).

    CAS  PubMed  Google Scholar 

  15. Arenas, E., Trupp, M., Akerud, P. & Ibañez, C. Neuron 15, 1465–1473 (1995).

    Article  CAS  Google Scholar 

  16. Schuchardt, A. et al. Nature 367, 380–383 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Pachnis, V., Mankoo, B. & Costantini, F. Development 119, 1005–1017 (1993).

    CAS  Google Scholar 

  18. Durbec, P. L. et al. Development 122, 349–358 (1996).

    CAS  Google Scholar 

  19. Torres, M., Gomez-Pardo, E., Dressler, G. R. & Gruss, P. Development 121, 4057–4065 (1995).

    CAS  PubMed  Google Scholar 

  20. Kreidberg, J. A. et al. Cell 74, 679—691 (1993).

    Article  CAS  Google Scholar 

  21. Swiatek, P. J. & Gridley, T. Genes Dev 7, 2071–2984 (1993).

    Article  CAS  Google Scholar 

  22. Tybulewicz, V. L. et al. Cell 65, 1153–1163 (1991).

    Article  CAS  Google Scholar 

  23. Wurst, W. & Joyner, A. L. in Gene Targeting: a Practical Approach (ed. Joyner, A. L.) 33–61 (IRL, Oxford, 1995).

    Google Scholar 

  24. Papaioannou, V. & Johnson, R. in Gene Targeting: a Practical Approach (ed. Joyner, A. L.) 107–146 (IRL, Oxford, 1995).

    Google Scholar 

  25. Gossler, A. & Zachgo, J. in Gene Targeting: a Practical Approach (ed. Joyner, A. L.) 181–225 (IRL, Oxford, 1995).

    Google Scholar 

  26. Butcher, L. L. & Woolf, N. J. in Handbook of Chemical Neuroanatomy Vol II (eds Bjorkland, A., Hokfelt, T. & Kuhar, M. J.) Elsevier, Amsterdam, 1984).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sánchez, M., Silos-Santiago, I., Frisén, J. et al. Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382, 70–73 (1996). https://doi.org/10.1038/382070a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/382070a0

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