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Activation of humanα 1-antitrypsin gene in rat hepatoma × human fetal liver cell hybrids depends on presence of human chromosome 14

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Somatic Cell Genetics

Abstract

In order to study the involvement of human chromosomes in the expression of liver-specific functions, we have produced somatic cell hybrids between a rat hepatoma (7777) cell line and human diploid skin fibroblasts (series XIX) or human fetal liver cells (series XXII). Production of human serum proteins was detected by immunoelectrophoretic analyses of concentrated serum-free hybrid culture supernatants. Human α1-antitrypsin (AAT) was secreted by a subset of hybrids but not by the parental cells. The activated human AAT phenotype segregated concordantly with human chromosome 14 in 18 primarily HAT-selected and five azaguanine back-selected series XXII hybrids. All other chromosomes were excluded as playing a role in AAT expression. Therefore, the AAT gene PI is assigned to chromosome 14. This quasi-constitutive expression of a liver-specific function was not observed for the other serum proteins studied, nor was it seen in the skin fibroblast-derived hybrids (series XIX) although AAT was produced by some of them.

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Literature cited

  1. Kaighn, M.E., and Prince, A.M. (1971).Proc. Natl. Acad. Sci. U.S.A. 68:2396–2400.

    Google Scholar 

  2. Cassio, D., Hassoux, R., Dupiers, M., Uriel, J., and Weiss, M.C. (1980).J. Cell. Physiol. 104:295–308.

    Google Scholar 

  3. Peterson, J.A. (1976).Proc. Natl. Acad. Sci. U.S.A. 73:2056–2060.

    Google Scholar 

  4. Tse, T.P.H., Morris, H.P., and Taylor, J.M. (1978).Biochemistry 17:3121–3128.

    Google Scholar 

  5. Cassio, D., Weiss, M.C, Ott, M.-O., Sala-Trepat, J.M., Fries, J., and Erdos, T. (1981).Cell 27:351–358.

    Google Scholar 

  6. Capetanaki, Y.G., Flytzanis, C.N., and Alonso, A. (1982).Mol. Cell. Biol. 2:258–266.

    Google Scholar 

  7. Selten, G.C.M., Selten-Versteegen, A.M.E., and Yap, S.H. (1981).Biochem. Biophys. Res. Commun. 103:278–284.

    Google Scholar 

  8. Sorimachi, K., Niwa, A., and Yasumura, Y. (1981).Cell Struct. Funct. 6:61–68.

    Google Scholar 

  9. Davis, F.M., and Adelberg, E.A. (1973).Bacteriol. Rev. 37:197–214.

    Google Scholar 

  10. Davidson, R.L. (1974).Annu. Rev. Genet. 8:195–219.

    Google Scholar 

  11. Davidson, R.L., Ephrussi, B., and Yamamoto, K. (1966).Proc. Natl. Acad. Sci. U.S.A. 56:1437–1440.

    Google Scholar 

  12. Peterson, J.A., and Weiss, M.C. (1972).Proc. Natl. Acad. Sci. U.S.A. 69:571–575.

    Google Scholar 

  13. Thompson, E.B., and Gelehrter, T.D. (1971).Proc. Natl. Acad. Sci. U.S.A. 68:2589–2593.

    Google Scholar 

  14. Bertolotti, R., and Weiss, M.C. (1974).Differentiation 2:5–17.

    Google Scholar 

  15. Weiss, M.C., and Chaplain, M. (1971).Proc. Natl. Acad. Sci. U.S.A. 68:3026–3030.

    Google Scholar 

  16. Darlington, G.J., Rankin, J.K., and Schlanger, G. (1982).Somat. Cell Genet. 8:403–412.

    Google Scholar 

  17. Darlington, G.J., Bernhard, H.P., and Ruddle, F.H. (1974).Science 185:859–862.

    Google Scholar 

  18. Morris, H.P., and Wagner, B.P. (1968). InMethods in Cancer Research, Vol. 4, (ed.) Busch H. (Academic Press, New York), pp. 125–152.

    Google Scholar 

  19. Sell, S., and Morris, H.P. (1974).Cancer Res. 34:1413–1417.

    Google Scholar 

  20. Norwood, T.H., Zeigler, C.J., and Martin, G.M. (1976).Somat. Cell Genet. 2:263–270.

    Google Scholar 

  21. Littlefield, J.W. (1964).Science 145:709–710.

    Google Scholar 

  22. Francke, U., and Oliver, N. (1978).Hum. Genet. 45:137–165.

    Google Scholar 

  23. Francke, U., Busby, N., Shaw, D., Hansen, S., and Brown, M.G. (1976).Somat. Cell Genet. 2:27–40.

    Google Scholar 

  24. Meera Khan, P. (1971).Arch. Biochem. Biophys. 145:470–483.

    Google Scholar 

  25. Harris, H., and Hopkinson, D.A. (1976).Handbook of Enzyme Electrophoresis in Human Genetics, (North-Holland Pub. Co., Amsterdam).

    Google Scholar 

  26. Ouchterlony, O. (1953).Acta Pathol. Microbiol. Scand. 32:231–240.

    Google Scholar 

  27. Laurell, C.-B. (1966).Anal. Biochem. 15:45–52.

    Google Scholar 

  28. Weeke, B. (1973).Scand. J. Immunol. 2(Suppl 1):15–56.

    Google Scholar 

  29. Kurnit, D.M., Wallner Philipp, B., and Bruns, G.A.P. (1982).Cytogenet. Cell Genet. 34:282–288.

    Google Scholar 

  30. Szpirer, J., and Szpirer, C. (1975).Cell 6:53–60.

    Google Scholar 

  31. Brown, J.E., and Weiss, M.C. (1975).Cell 6:481–494.

    Google Scholar 

  32. Szpirer, J., and Szpirer, C. (1979).J. Cell Sci. 35:267–279.

    Google Scholar 

  33. Rankin, J.K., and Darlington, G.J. (1979).Somat. Cell Genet. 5:1–10.

    Google Scholar 

  34. Kielty, C.M., Povey, S., and Hopkinson, D.A. (1981).Ann. Hum. Genet. 45:341–356.

    Google Scholar 

  35. Wray, L.K., and Sutton, H.E. (1982).Somat. Cell Genet. 8:433–449.

    Google Scholar 

  36. Fagerhol, M.K., and Cox, D.W. (1981).Adv. Hum. Genet. 11:1–62.

    Google Scholar 

  37. Carrell, R.W., Jeppson, J.-O., Laurell, C.-B., Brennan, S.O., Owen, M.C., Vaughan, L., and Boswell, D.R. (1982).Nature 298:329–333.

    Google Scholar 

  38. DeMartinville, B., Wyman, A.R., White, R., and Francke, U. (1982).Am. J. Hum. Genet. 34:216–226.

    Google Scholar 

  39. Migone, N., Feder, J., Cann, H., van West, B., Hwang, J., Takahashi, N., Honjo, T., Piazza, A., and Cavalli-Sforza, L.L. (1983).Proc. Natl. Acad. Sci. U.S.A. 80:467–741.

    Google Scholar 

  40. Pearson, S., Tetri, P., and Francke, U. (1982).Cytogenet. Cell Genet. 32:309.

    Google Scholar 

  41. Gedde-Dahl, T., Jr., Fagerhol, M.K., Cook, P.J.L., and Noades, J. (1972).Ann. Hum. Genet. 35:393–399.

    Google Scholar 

  42. Croce, C.M., Shander, M., Martinis, J., Cicurel, L., D'Ancona, G.G., Dolby, T.W., and Koprowski, H. (1979).Proc. Natl. Acad. Sci. U.S.A. 76:3416–3419.

    Google Scholar 

  43. Smith, M., and Hirschhorn, K. (1978).Proc. Natl. Acad. Sci. U.S.A. 75:3367–3371.

    Google Scholar 

  44. Bennick, A., Gedde-Dahl, T., Jr., and Brogger, A. (1978).Cytogenet. Cell Genet. 22:661–665.

    Google Scholar 

  45. Hobart, M.J., Rabbitts, T.H., Goodfellow, P.N., Solomon, E., Chambers, S., Spurr, N., and Povey, S. (1981).Ann. Hum. Genet. 45:331–335.

    Google Scholar 

  46. Kirsch, I.R., Morton, C.C., Nakahara, K., and Leder, P. (1982).Science 216:301–303.

    Google Scholar 

  47. Cox, D.W., Markovic, V.D., and Teshima, I.E. (1982).Nature 297:428–430.

    Google Scholar 

  48. Darlington, G.J., Astrin, K.H., Muirhead, S.P., Desnick, R.J., and Smith, M. (1982).Cytogenet. Cell Genet. 32:262–263.

    Google Scholar 

  49. Darlington, G.J., Astrin, K.H., Muirhead, S.P., Desnick, R.J., and Smith, M. (1982).Proc. Natl. Acad. Sci. U.S.A. 79:870–873.

    Google Scholar 

  50. Turner, B.M., and Turner, V.S. (1980).Somat. Cell Genet. 6:1–14.

    Google Scholar 

  51. Gedde-Dahl, T., Jr., Frants, R.R., Olaisen, B., Eriksson, A.W., Van Loghen, E., and Lamm, L. (1981).Ann. Hum. Genet. 45:143–153.

    Google Scholar 

  52. Kurachi, K., Chandra, T., Friezner Degen, S.J., White, T.T., Marchioro, T.L., Woo, S.L.C., and Davie, E.W. (1981).Proc. Natl. Acad. Sci. U.S.A. 78:6826–6830.

    Google Scholar 

  53. Pearson, P.L., Roderick, T.H., Davisson, M.T., Lalley, P.A., and O'Brien, S.J. (1982).Cytogenet. Cell Genet. 32:208–220.

    Google Scholar 

  54. Taylor, B.A., Bailey, D.W., Cherry, M., Riblet, R., and Weigert, M. (1975).Nature 256:644–646.

    Google Scholar 

  55. Meo, T., Johnson, J., Beechey, C.V., Andrews, J.P., and Searle, A.G. (1980).Proc. Natl. Acad. Sci. U.S.A. 77:550–553.

    Google Scholar 

  56. Wilcox, F.H. (1975).J. Hered. 66:19–22.

    Google Scholar 

  57. Myerowitz, R.L., Chrambach, A., Rodbard, D., and Robbins, J.B. (1972).Anal. Biochem. 48:394–409.

    Google Scholar 

  58. Leicht, M., Long, G.L., Chandra, T., Kurachi, K., Kidd, V.J., Mace, M., Jr., Davie, E.W., and Woo, S.L.C. (1982).Nature 297:655–659.

    Google Scholar 

  59. Taggart, R.T., Tetri, P., and Francke, U. (1980).Somat. Cell Genet. 6:769–776.

    Google Scholar 

  60. Papaconstantinou, J., Wong, E., Ratrie, H., Szpirer, C., and Szpirer, J. (1982).Somat. Cell Genet. 8:363–376.

    Google Scholar 

  61. Darlington, G.J., Papaconstantinou, J., Sammons, D.W., Brown, P.C., Wong, E.Y., Esterman, A.L., and Kang, J. (1982).Somat. Cell Genet. 8:451–464.

    Google Scholar 

  62. Sperling, L., and Weiss, M.C. (1980).Proc. Natl. Acad. Sci. U.S.A. 77:3412–3416.

    Google Scholar 

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Authors and Affiliations

  1. Departments of Human Genetics and Pediatrics, Yale University School of Medicine, P.O. Box 3333, 06510, New Haven, Connecticut

    S. J. Pearson, P. Tetri & U. Francke

  2. Department of Human Genetics, University of Pennsylvania School of Medicine, 19104, Philadelphia, Pennsylvania

    D. L. George

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  2. P. Tetri
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  3. D. L. George
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  4. U. Francke
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Pearson, S.J., Tetri, P., George, D.L. et al. Activation of humanα 1-antitrypsin gene in rat hepatoma × human fetal liver cell hybrids depends on presence of human chromosome 14. Somat Cell Mol Genet 9, 567–592 (1983). https://doi.org/10.1007/BF01574259

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  • DOI: https://doi.org/10.1007/BF01574259

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