Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL (original) (raw)

Nature volume 373, pages 432–434 (1995)Cite this article

Abstract

CHROMOSOMAL translocations associated with malignancies often result in deregulated expression of genes encoding transcription factors1. In human T-cell leukaemias such regulators belong to diverse protein families and may normally be expressed widely (for example, Ttg-1/rbtnl, Ttg-2/rbtn2) 2,3, exclusively outside the haematopoietic system (for example, Hoxll) 4, or specifically in haematopoietic cells and other selected sites (for example, tal-1/ SCL, lyl-1) 5,6. Aberrant expression within T cells is thought to interfere with programmes of normal maturation. The most frequently activated gene in acute T-cell leukaemias, tal-1 (also called SCL) 7,8, encodes a candidate regulator of haematopoietic development9, a basic-helix-loop-helix protein5, related to critical myogenic10 and neurogenic11 factors. Here we show by targeted gene disruption in mice12 that tal-1 is essential for embryonic blood formation in vivo. With respect to embryonic erythropoiesis, tal-1 deficiency resembles loss of the erythroid transcription factor GATA-113,14 or the LIM protein rbtn215 .Profound reduction in myeloid cells cultured in vivo from tal-1 null yolk sacs suggests a broader defect manifest at the myelo-erythroid or multipotential progenitor cell level.

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

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

References

  1. Rabbitts, T. H. Nature 372, 143–149 (1994).
    Article ADS CAS Google Scholar
  2. Boehm, T. et al. EMBO J. 7, 385–394 (1988).
    Article CAS Google Scholar
  3. Royer-Pokora, B., Loos, U. & Ludwig, W.-D. Oncogene 6, 1887–1893 (1991).
    CAS PubMed Google Scholar
  4. Roberts, C. W. M., Shutter, J. R. & Korsmeyer, S. J. Nature 368, 747–749 (1994).
    Article ADS CAS Google Scholar
  5. Begley, C. G. et al. Proc. natn. Acad. Sci. U.S.A. 86, 10128–10132 (1989).
    Article ADS CAS Google Scholar
  6. Mellentin, J. D., Smith, S. D. & Cleary, M. L. Cell 58, 77–83 (1989).
    Article CAS Google Scholar
  7. Brown, L. et al. EMBO J. 9, 3343–3551 (1990).
    Article CAS Google Scholar
  8. Aplan, P. D. et al. Science 250, 1426–1429 (1990).
    Article ADS CAS Google Scholar
  9. Visvader, J., Begley, C. G. & Adams, J. M. Oncogene 6, 187–194 (1991).
    CAS PubMed Google Scholar
  10. Olson, E. N. & Klein, W. H. Genes Dev. 8, 1–8 (1994).
    Article CAS Google Scholar
  11. Guillemot, F. et al. Cell 75, 463–476 (1993).
    Article CAS Google Scholar
  12. Capecchi, M. R. Science 244, 1288–1292 (1989).
    Article ADS CAS Google Scholar
  13. Pevny, L. et al. Nature 349, 257–260 (1991).
    Article ADS CAS Google Scholar
  14. Weiss, M. J., Keller, G. & Orkin, S. H. Genes Dev. 8, 1184–1197 (1994).
    Article CAS Google Scholar
  15. Warren, A. J. et al. Cell 78, 45–57 (1994).
    Article CAS Google Scholar
  16. Tsai, S. F. et al. Nature 339, 446–51 (1989).
    Article ADS CAS Google Scholar
  17. Mucenski, M. L. et al. Cell 65, 677–689 (1991).
    Article CAS Google Scholar
  18. Wong, P. M. C., Chung, S. W., Chui, D. H. K. & Eaves, C. J. Proc. natn. Acad. Sci. U.S.A. 83, 3851–3854 (1986).
    Article ADS CAS Google Scholar
  19. Rudnicki, M. A. et al. Cell 75, 1351–1359 (1993).
    Article CAS Google Scholar
  20. Aplan, P. D., Nakahara, K., Orkin, S. H. & Kirsch, I. R. EMBO J. 11, 4073–4081 (1992).
    Article CAS Google Scholar
  21. Kallianpur, A. R., Jordan, J. E. & Brandt, S. J. Blood 83, 1200–1208 (1994).
    CAS PubMed Google Scholar
  22. Hwang, L.-Y., Siegelman, M., Davis, L., Oppenheimer-Marks, N. & Baer, R. Oncogene 8, 3043–3046 (1993).
    CAS PubMed Google Scholar
  23. Valge-Archer, V. E. et al. Proc. natn. Acad. Sci. U.S.A. 91, 8617–8621 (1994).
    Article ADS CAS Google Scholar
  24. Tybulewicz, V. L. J., Crawford, C. E., Jackson, P. K., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).
    Article CAS Google Scholar
  25. Ausubel, F. M. et al. Curr. Prot. molec. Biol. (1987).
  26. Begley, C. G. et al. Proc. natn. Acad. Sci. U.S.A. 88, 869–873 (1991).
    Article ADS CAS Google Scholar
  27. Li, E., Bestor, T. H. & Jaenisch, R. Cell 69, 915–926 (1992).
    Article CAS Google Scholar
  28. Tsai, F.-Y. et al. Nature 371, 221–226 (1994).
    Article ADS CAS Google Scholar
  29. Chomczynski, P. & Sacchi, N. Analyt. Biochem. 162, 156–159 (1987).
    Article CAS Google Scholar
  30. Keller, G., Kennedy, M., Papayannopoulou, T. & Wiles, M. V. Molec. cell. Biol. 13, 472–486 (1993).
    Article Google Scholar

Download references

Author information

Author notes

  1. Stuart H. Orkin: To whom correspondence should be addressed.

Authors and Affiliations

  1. Division of Hematology/Oncology, Children's Hospital and the Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School,
    Ramesh A. Shivdasani, Erica L. Mayer & Stuart H. Orkin
  2. Howard Hughes Medical Institute, Boston, Massachusetts, 02115, USA
    Ramesh A. Shivdasani, Erica L. Mayer & Stuart H. Orkin

Authors

  1. Ramesh A. Shivdasani
    You can also search for this author inPubMed Google Scholar
  2. Erica L. Mayer
    You can also search for this author inPubMed Google Scholar
  3. Stuart H. Orkin
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Shivdasani, R., Mayer, E. & Orkin, S. Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL.Nature 373, 432–434 (1995). https://doi.org/10.1038/373432a0

Download citation

This article is cited by