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Developmental regulation of a cloned adult β-globin gene in transgenic mice

Abstract

At different stages of mammalian development, distinct embryonic, fetal and adult haemoglobins are synthesized in erythroid cells, a process termed haemoglobin switching. The cellular and molecular mechanisms controlling haemoglobin switching have been intensively studied, but remain poorly understood1. To study the developmental regulation of globin gene expression, we have produced transgenic mice2–6 in which cloned globin genes are present in erythroid cells throughout development. Recently, we reported that adult mice in several transgenic lines carrying a hybrid mouse/human adult β-globin gene, expressed the gene in a correct tissue-specific manner7. This finding raised the question of whether an exogenous globin gene could also be subject to appropriate stage-specific regulation. We report here that the hybrid β-globin gene, like the endogenous adult β-globin genes, is inactive in yolk sac-derived embryonic erythroid cells and is expressed for the first time in fetal liver erythroid cells. Our results indicate that a stage-specific pattern of expression can be conferred by cis- acting regulatory elements closely linked to an adult β-globin gene. They also suggest that the embryonic and adult β-globin genes in the mouse are activated (or repressed) by distinct trans-acting regulatory factors present in embryonic, fetal and adult erythroid cell.

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References

  1. Stamatoyannopoulos, G. & Neinhuis, A. W. (eds) Globin Gene Expression and Hematopoietic Differentiation (Liss, New York, 1983).

  2. Gordon, J., Scangos, G. A., Plotkin, D. J., Barbosa, J. A. & Ruddle, F. H. Proc. natn. Acad. Sci. U.S.A. 77, 7380–7384 (1980).

    Article  ADS  CAS  Google Scholar 

  3. Wagner, E. F., Stewart, T. A. & Mintz, B. Proc. natn. Acad. Sci. U.S.A. 78, 5016–5020 (1981).

    Article  ADS  CAS  Google Scholar 

  4. Costantini, F. & Lacy, E. Nature 294, 92–94 (1981).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Brinster, R. L. et al. Cell 27, 223–231 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lacy, E., Roberts, S., Evans, E. P., Burtenshaw, M. D. & Costantini, F. D. Cell 34, 343–358 (1983).

    Article  CAS  PubMed  Google Scholar 

  7. Chada, K. et al. Nature 314, 377–380 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Russell, E. S. Adv. Genet. 20, 357–459 (1979).

    Article  CAS  PubMed  Google Scholar 

  9. Craig, M. L. & Russell, E. S. Devl Biol. 10, 191–201 (1964).

    Article  CAS  Google Scholar 

  10. Fantoni, A., Bank, A. & Marks, P. A. Science 157, 1327–1328 (1967).

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Barker, J. E. Devl Biol. 18, 14–29 (1968).

    Article  CAS  Google Scholar 

  12. Gilman, J. G. & Smithies, O. Science 160, 885–886 (1968).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Hansen, J. N., Konkel, D. A. & Leder, P. J. biol. Chem. 257, 1048–1052 (1982).

    CAS  PubMed  Google Scholar 

  14. Farace, M. G. et al. J. biol. Chem. 259, 7123–7128 (1984).

    CAS  PubMed  Google Scholar 

  15. Brotherton, T. W., Chui, D. H. K., Gauldie, J. & Patterson, M. Proc. natn. Acad. Sci. U.S.A. 76, 2853–2857 (1979).

    Article  ADS  CAS  Google Scholar 

  16. Brotherton, T. W., Chui, D. H. K., McFarland, E. C. & Russell, E. S. Blood 54, 673–683 (1979).

    CAS  PubMed  Google Scholar 

  17. Johnson, G. R. & Jones, R. O. J. Embryol. exp. Morph. 30, 83–96 (1973).

    CAS  PubMed  Google Scholar 

  18. Kovach, J. S., Marks, P. A., Russell, E. S. & Epler, H. J. molec. Biol. 25, 131–142 (1967).

    Article  CAS  PubMed  Google Scholar 

  19. Rifkind, R. A., Chui, D. H. K. & Epler, H. J. Cell Biol. 40, 343–365 (1969).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Weatherall, D. J. & Clegg, J. B. The Thalassaemia Syndromes (Blackwell, Oxford, 1981).

    Google Scholar 

  21. Chao, M. V., Mellon, P., Charnay, P., Maniatis, T. & Axel, R. Cell 32, 483–493 (1983).

    Article  CAS  PubMed  Google Scholar 

  22. Berk, A. J. & Sharp, P. A. Cell 12, 721–732 (1977).

    Article  CAS  PubMed  Google Scholar 

  23. Weaver, R. & Weissman, C. Nucleic Acids Res. 7, 1175–1193 (1979).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Maxam, A. M. & Gilbert, W. Meth. Enzym. 65, 499–560 (1980).

    Article  CAS  PubMed  Google Scholar 

  25. Wright, S., deBoer, E., Grosveld, F. G. & Flavell, R. A. Nature 305, 333–336 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  26. Charnay, P. et al. Cell 38, 251–263 (1984).

    Article  CAS  PubMed  Google Scholar 

  27. Wright, S., Rosenthal, A., Flavell, R. & Grosveld, F. Cell 38, 265–273 (1984).

    Article  CAS  PubMed  Google Scholar 

  28. Young, K. et al. Proc. natn. Acad. Sci. U.S.A. 81, 5315–5319 (1984).

    Article  ADS  CAS  Google Scholar 

  29. Wold, B. et al. Proc. natn. Acad. Sci. U.S.A. 76, 5684–5688 (1979).

    Article  ADS  CAS  Google Scholar 

  30. Mantei, N., Boll, W. & Weissman, C. Nature 281, 40–46 (1979).

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Collins, F. S. & Weissman, S. M. Prog. Nucleic Acid Res. molec. Biol 31, 315–462 (1984).

    Article  CAS  Google Scholar 

  32. Stadler, J. et al. Cell 20, 451–460 (1980).

    Article  Google Scholar 

  33. Weintraub, H., Larsen, A. & Groudine, M. Cell 24, 333–344 (1981).

    Article  CAS  PubMed  Google Scholar 

  34. Chirgwin, J., Przybyla, A., MacDonald, R. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).

    Article  CAS  PubMed  Google Scholar 

  35. Lehrach, H., Diamond, D., Wozney, J. M. & Boedtker, H. Biochemistry 16, 4743–4751 (1977).

    Article  CAS  PubMed  Google Scholar 

  36. Humphries, S., Windass, J. & Williamson, R. Cell 7, 267–277 (1976).

    Article  CAS  PubMed  Google Scholar 

  37. Rougeon, F. & Mach, B. Gene 1, 229–239 (1977).

    Article  CAS  PubMed  Google Scholar 

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Magram, J., Chada, K. & Costantini, F. Developmental regulation of a cloned adult β-globin gene in transgenic mice. Nature 315, 338–340 (1985). https://doi.org/10.1038/315338a0

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