Skip to main content

Tissue-specific extinguisher loci in the murine genome: A screening study based on a rat/mouse microcell hybrid panel

Abstract

Extinction of tissue-specific traits in intertypic somatic cell hybrids is a well-known phenomenon. In the past few years, microcell hybrids have been used in attempts to dissect this phenotype genetically, and tissue-specific extinguisher loci have been mapped to two different mouse chromosomes. When transferred from fibroblasts into hepatoma cells by microcell fusion, these loci down-regulate expression of specific liver genes intrans. However, other liver genes that are extinguished in genotypically complete hybrids seem not to be extinguished in monochromosomal hybrids. To assess the generality of monochromosomal extinction phenotypes, we assembled a collection of rat hepatoma/mouse fibroblast microcell hybrids that represent most of the mouse chromosome complement, and we screened them for expression of a large number of liver-specific genes. Phosphoenolpyruvate carboxykinase gene expression was down-regulated in hybrids containing mouse chromosome 7 or mouse chromosome 11, but other extinction phenotypes were not readily apparent. These results indicate that extinction of many liver genes may be a polygenic trait.

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

Literature Cited

  1. Gourdeau, H., and Fournier, R.E.K. (1990).Annu. Rev. Cell Biol. 6:69–94.

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  3. Davidson, R.L., Ephrussi, B., and Yamamoto, L. (1968).J. Cell. Physiol. 72:115–127.

    Article  PubMed  Google Scholar 

  4. Bertolotti, R., and Weiss, M.C. (1972a).J. Cell Physiol. 79:211–224.

    Article  PubMed  Google Scholar 

  5. Bertolotti, R., and Weiss, M.C. (1972b).Biochimie 54:195–201.

    PubMed  Google Scholar 

  6. Schneider, J.A., and Weiss, M.C. (1971).Proc. Natl. Acad. Sci. U.S.A. 68:127–131.

    PubMed  Google Scholar 

  7. Sparkes, R.S., and Weiss, M.C. (1973).Proc. Natl. Acad. Sci. U.S.A. 70:377–381.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  9. Weiss, M.C., Sparkes, R.S., and Bertolotti, R. (1975).Somat. Cell Genet. 1:27–40.

    Article  PubMed  Google Scholar 

  10. Killary, A.M., and Fournier, R.E.K. (1984).Cell 38:523–534.

    Article  PubMed  Google Scholar 

  11. Lem, J., Chin, A.C., Thayer, M.J., Leach, R.J., and Fournier, R.E.K. (1988).Proc. Natl. Acad. Sci. U.S.A. 85:7302–7306.

    PubMed  Google Scholar 

  12. Thayer, M.J., and Fournier, R.E.K. (1989).Mol. Cell. Biol. 9:2837–2846.

    PubMed  Google Scholar 

  13. Ruppert, S., Boshart, M., Bosch, F.X., Schmid, W., Fournier, R.E.K., and Schutz, G. (1990).Cell 61:895–904.

    Article  PubMed  Google Scholar 

  14. Nebes, V.L., and Morris, S.M. (1988).Mol. Endo 2:444–451.

    Google Scholar 

  15. Sasaki, K., Kripe, P.P., Koch, S.R.K., Andreone, T.L., Petersen, D.D., Beale, E.G., and Granner, D. (1984).J. Biol. Chem. 259:15242–15251.

    PubMed  Google Scholar 

  16. Schmid, E., Schmid, W., Jantsen, M., Mayer, D., Jastroff, B., and Schutz, G. (1987).Eur. J. Biochem. 165:499–506.

    Article  PubMed  Google Scholar 

  17. Ip, Y.T., Fournier, R.E.K., and Chalkley, R. (1990).Mol. Cell. Biol. 10:3782–3787.

    PubMed  Google Scholar 

  18. Boshart, M., Weih, F., Schmidt, A., Fournier, R.E.K., and Schutz, G. (1990).Cell 61:905–916.

    Article  PubMed  Google Scholar 

  19. Schafer, A.J., and Fournier, R.E.K. (1992).Somat. Cell Mol. Genet. 18:571–581.

    Article  PubMed  Google Scholar 

  20. Jones, K.W., Chevrette, M., Shapero, M.H., and Fournier, R.E.K. (1991).Cell 66:861–872.

    Article  PubMed  Google Scholar 

  21. Boshart, M., Weih, F., Nichols, M., and Schutz, G. (1991).Cell 66:849–859.

    Article  PubMed  Google Scholar 

  22. Chin, A.C., and Fournier, R.E.K. (1989).Mol. Cell. Biol. 9:3736–3743.

    PubMed  Google Scholar 

  23. Petit, C., Levilliers, J., Ott, M.O., and Weiss, M.C. (1986).Proc. Natl. Acad. Sci. U.S.A. 83:2561–2565.

    PubMed  Google Scholar 

  24. Cerosaletti, K., and Fournier, R.E.K. (1994). (submitted).

  25. Killary, A.M., Lugo, T.G., and Fournier, R.E.K. (1984).Bioch. Genet. 22:201–213.

    Article  Google Scholar 

  26. Peterson, T.C., Killary, A.M., and Fournier, R.E.K. (1985).Mol. Cell. Biol. 5:2491–2494.

    PubMed  Google Scholar 

  27. Fournier, R.E.K., and Frelinger, J.A. (1982).Mol. Cell. Biol. 2:539–552.

    Google Scholar 

  28. Lem, J., and Fournier, R.E.K. (1985).Somat. Cell Mol. Genet. 11:633–638.

    Article  PubMed  Google Scholar 

  29. Bulla, G., DeSimone, V., Cortese, R., and Fournier, R.E.K. (1992).Genes Dev. 6:316–327.

    PubMed  Google Scholar 

  30. Chen, T.R. (1977).Exp. Cell Res. 104:255–262.

    Google Scholar 

  31. Chin, A.C. (1987).PhD thesis. University of Southern California.

  32. Killary, A.M., Leach, R.J., Moran, R.G., and Fournier, R.E.K. (1986).Somat. Cell Mol. Genet. 12:641–648.

    Article  PubMed  Google Scholar 

  33. Church, G.M., and Gilbert, W. (1984).Proc. Natl. Acad. Sci. U.S.A. 81:1991–1995.

    PubMed  Google Scholar 

  34. Maniatis, T., Fritsch, E.F., and Sambrook, J. (1982).Molecular Cloning: A Laboratory Manual. (Cold Spring Harboour Laboratory, Cold Spring Harbor, New York), pp. 383–386.

    Google Scholar 

  35. Bell, G.I., Karam, J.H., and Rutter, W.J. (1981).Proc. Natl. Acad. Sci. U.S.A. 78:5759–5763.

    PubMed  Google Scholar 

  36. Capanna, E., Gropp, A., Winking, H., Noack, G., and Civitelli, M.-V. (1976).Chromosoma (Berlin) 58:341–353.

    Article  Google Scholar 

  37. Leach, R.J., Thayer, M.J., Schafer, A.J., and Fournier, R.E.K. (1989).Genomics 5:167–176.

    Article  PubMed  Google Scholar 

  38. Edenberg, H.J., Zhang, K., Fon, K., Bosron, W.F., and Li, T.K. (1985).Proc. Natl. Acad. Sci. U.S.A. 82:2262–2266.

    PubMed  Google Scholar 

  39. Sargent, T.D., Wu, J.R., Sala-Trepat, J.M., Wallace, R.B., Reyes, A.A., and Bonner, J. (1979).Proc. Natl. Acad. Sci. U.S.A. 76:3256–3260.

    PubMed  Google Scholar 

  40. Simon, M.-P., Besmond, C., Cottreau, D., Weber, A., Chaumet-Riffaud, P., Dreyfus, J.-C., Trepat, J.S., Marie, J., and Kahn, A. (1983).J. Biol. Chem. 258:14576–14584.

    PubMed  Google Scholar 

  41. Kawamoto, S., Amaya, Y., Murakami, K., Tokunaga, F., Iwanaga, S., Kobayashi, K., Saheki, T., Kimura, S., and Mori, M. (1987).J. Biol. Chem. 262:6280–6283.

    PubMed  Google Scholar 

  42. Amaya, Y., Matsubasa, T., Takiguchi, M., Kobayashi, K., Saheki, T., Kawamoto, S., and Mori, M. (1988).J. Biochem. 103:177–181.

    PubMed  Google Scholar 

  43. Surh, L.C., Morris, S.M., O'Brien, W.E., and Beaudet, A.L. (1988).Nucleic Acids Res. 16:9352.

    PubMed  Google Scholar 

  44. Degen, S.J., Shaefer, L.A., Jamison, C.S., Grant, S.G., Fitzgibbon, J.J., Pai, J.A., Chapman, V.M., and Elliot, R.W. (1990).DNA Cell Biol. 9:487–498.

    PubMed  Google Scholar 

  45. Turcotte, B., Guertin, M., Chevrette, M., and Belanger, L. (1985).Nucleic Acids Res. 13:2387–2398.

    PubMed  Google Scholar 

  46. Crabtree, G.R., and Kant, J.A. (1981).J. Biol. Chem. 256:9718–9723.

    PubMed  Google Scholar 

  47. Frain, M., Swart, G., Monaci, P., Stampfli, S., Frank, R., and Cortese, R. (1989).Cell 59:145–157.

    Article  PubMed  Google Scholar 

  48. Derman, E., Krauter, K., Walling, L., Weinberger, C., Ray, M., and Darnell, J.E. (1981).Cell 23:731–739.

    Article  PubMed  Google Scholar 

  49. Yoo-Warren, H., Monahan, J.E., Short, J., Short, H., Bruzel, A., Wynshaw-Boris, A., Heisner, H.M., Samols, D., and Hanson, R.W. (1983).Proc. Natl. Acad. Sci. U.S.A. 80:3656–3660.

    PubMed  Google Scholar 

  50. Scherer, G., Schmid, W., Strange, C.M., Rowekamp, W., and Schutz, G. (1982).Proc. Natl. Acad. Sci. U.S.A. 79:7205–7208.

    PubMed  Google Scholar 

  51. Cowan, N.J., Dobner, P.R., Fuchs, E.V., and Cleveland, D.W. (1983).Mol. Cell. Biol. 3:1738–1745.

    PubMed  Google Scholar 

  52. Gebhard, W., and Zachau, H.G. (1982).J. Mol. Biol. 157:453–471.

    Article  PubMed  Google Scholar 

  53. Fournier, R.E.K., and Ruddle, F.H. (1977).Proc. Natl. Acad. Sci. U.S.A. 74:319–323.

    PubMed  Google Scholar 

  54. Shapero, M., Langston, A.A., and Fournier, R.E.K. (1994).Somat. Cell Mol. Genet. 20:215–231.

    PubMed  Google Scholar 

  55. Boshart, M., Nitsch, D., and Schutz, G. (1993)Trends Genet. 9:240–245.

    Article  PubMed  Google Scholar 

  56. Bulla, G.A., and Fournier, R.E.K. (1992).Somat. Cell Mol. Genet. 18:361–370.

    Article  PubMed  Google Scholar 

  57. Bulla, G.A., and Fournier, R.E.K. (1994).Mol. Cell Biol. (in press).

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Schafer, A.J., Bulla, G.A. & Fournier, R.E.K. Tissue-specific extinguisher loci in the murine genome: A screening study based on a rat/mouse microcell hybrid panel. Somat Cell Mol Genet 20, 195–213 (1994). https://doi.org/10.1007/BF02254760

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02254760

Keywords

  • Hepatoma Cell
  • Cell Hybrid
  • Mouse Chromosome
  • Chromosome Complement
  • Somatic Cell Hybrid