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.

A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin μ chain gene

Abstract

OF the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (μ chain), but not light chains1. Recent data suggest that pre-B cells express μ chains on the membrane together with the 'surrogate' light chains λ5 and VpreB (refs 2–7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes8. We have now assessed the importance of the membrane form of the μ chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the μ-chain constant region by gene targeting9 in mouse embryonic stem cells10. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation.

References

  1. 1

    Cooper, M. D. & Burrows, P. D. in Immunoglobulin Genes (eds Honjo, T., Alt, F. W. & Rabbitts, T. H.) 1–21 (Academic, London, 1989).

    Google Scholar 

  2. 2

    Pillai, P. & Baltimore, D. Nature 329, 172–174 (1987).

    ADS  CAS  Article  Google Scholar 

  3. 3

    Kerr, W. G., Cooper, M. D., Feng, L. & Hendershot, L. M. Int. Immun. 1, 355–361 (1989).

    CAS  Article  Google Scholar 

  4. 4

    Takemori, T. et al. EMBO J. 9, 2493–2500 (1990).

    CAS  Article  Google Scholar 

  5. 5

    Tsubata, T. & Reth, M. J. exp. Med. 172, 973–976 (1990).

    CAS  Article  Google Scholar 

  6. 6

    Sakaguchi, N. & Melchers, F. Nature 324, 579–582 (1986).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Kudo, A. & Melchers, F. EMBO J. 6, 2267–2272 (1987).

    CAS  Article  Google Scholar 

  8. 8

    Reth, M., Petrac, E., Wiese, P., Lobel, L. & Alt, F. W. EMBO J. 6, 3299–3305 (1987).

    CAS  Article  Google Scholar 

  9. 9

    Capecchi, M. R. Science 244, 1288–1292 (1989).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Evans, M. J. & Kaufman, M. H. Nature 292, 154–156 (1981).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Thomas, K. R. & Capecchi, M. R. Cell 51, 503–512 (1987).

    CAS  Article  Google Scholar 

  12. 12

    Mansour, S. L., Thomas, K. R. & Capecchi, M. R. Nature 336, 348–352 (1988).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Doetschmann, T. C., Eistetter, M., Katz, M., Schmidt, W. & Kemler, R. J. J. Embryol. exp. Morph. 87, 27–45 (1985).

    Google Scholar 

  14. 14

    Robertson, E. J. in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach (ed. Robertson, E. J.) 71–112 (IRL, Oxford, 1987).

    Google Scholar 

  15. 15

    Coffman, R. L. & Weissman, I. L. Nature 289, 681–683 (1981).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Manz, J., Denis, K., Witte, O., Brinster, R. & Storb, U. J. exp. Med. 168, 1363–1381 (1988).

    CAS  Article  Google Scholar 

  17. 17

    Förster, I., Vieira, P. & Rajewsky, K. Int. Immun. 1, 321–331 (1989).

    Article  Google Scholar 

  18. 18

    Opstelten, D. & Osmond, D. G. J. Immun. 131, 2635–2640 (1983).

    CAS  Google Scholar 

  19. 19

    Coffman, R. L. & Weissman, I. L. J. molec. cell. Immun. 1, 31–38 (1983).

    CAS  Google Scholar 

  20. 20

    Osmond, D. G. Immunol. Rev. 93, 103–124 (1986).

    CAS  Article  Google Scholar 

  21. 21

    Cooper, M. D. & Butler, J. L. in Fundamental Immunology 2nd edn (ed. Paul, W. E.) 1033–1058 (Raven, New York, 1989).

    Google Scholar 

  22. 22

    Guise, J. W., Galli, G., Nevins, J. R. & Tucker, P. W. in Immunoglobulin Genes (eds Honjo, T., Alt, F. W. & Rabbitts, T. H.) 275–301 (Academic, London, 1989).

    Google Scholar 

  23. 23

    Kim, H.-S. & Smithies, O. Nucleic Acids Res. 16, 8887–8903 (1988).

    CAS  Article  Google Scholar 

  24. 24

    Coffmen, R. L. Immunol. Rev. 69, 5–23 (1982).

    Article  Google Scholar 

  25. 25

    Schüppl, R., Wilke, J. & Weiler, E. Eur. J. Immunol. 17, 739–741 (1987).

    Article  Google Scholar 

  26. 26

    Nishikawa, S., Sasaki, Y., Kina, T., Amagi, T. & Katsura, Y. Immunogenetics 23, 137–139 (1986).

    CAS  Article  Google Scholar 

  27. 27

    Opitz, H. G. et al. Immunobiology 160, 438–453 (1982).

    CAS  Article  Google Scholar 

  28. 28

    Leo, O., Foo, M., Sachs, D. H., Samelson, L. E. & Bluestone, J. A. Proc. natn. Acad. Sci. U.S.A. 84, 1374–1378 (1987).

    ADS  CAS  Article  Google Scholar 

  29. 29

    Grützmann, R. thesis, Univ. Cologne (1981).

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kitamura, D., Roes, J., Kühn, R. et al. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin μ chain gene. Nature 350, 423–426 (1991). https://doi.org/10.1038/350423a0

Download citation

Further reading

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