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Profound block in thymocyte development in mice lacking p56lck

Nature volume 357, pages 161–164 (1992)Cite this article

Abstract

THE protein Lck (p56lck) has a relative molecular mass of 56,000 and belongs to the Src family of tyrosine kinases1–3. It is expressed exclusively in lymphoid cells, predominantly in thymocytes and peripheral T cells4,5. Lck associates specifically with the cytoplasmic domains of both CD4 and CD8 T-cell surface glycoproteins6,7 and interacts with the β-chain of the interleukin-2 receptor8, which implicates Lck activity in signal transduction during thymocyte ontogeny9–13 and activation of mature T cells14–19. Here we generate an lck null mutation by homologous recombination in embryonic stem cells to evaluate the role of p56lck in T-cell development and activation. Lck-deficient mice show a pronounced thymic atrophy, with a dramatic reduction in the double-positive (CD4+CD8+) thymocyte population. Mature, single-positive thymocytes are not detectable in these mice and there are only very few peripheral T cells. These results illustrate the crucial role of this T-cell-specific tyrosine kinase in the thymocyte development.

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References

  1. Marth, J. D., Peet, R., Krebs, E. G. & Perlmutter, R. M. Cell 43, 393–404 (1985).

    Article  CAS  Google Scholar 

  2. Koga, Y. et al. Eur. J. Immun. 16, 1643–1646 (1986).

    Article  CAS  Google Scholar 

  3. Voronova, A. F. & Sefton, B. M. Nature 319, 682–686 (1986).

    Article  ADS  CAS  Google Scholar 

  4. Perlmutter, R. M. et al. J. cell Biochem. 38, 117–126 (1988).

    Article  CAS  Google Scholar 

  5. Veillette, A., Abraham, N., Caron, L. & Davidson, D. Semin. Immun. 3, 143–152 (1991).

    CAS  Google Scholar 

  6. Veillette, A., Bookman, M. A., Horak, E. M. & Bolen, J. B. Cell 55, 301–308 (1988).

    Article  CAS  Google Scholar 

  7. Shaw, A. S. et al. Cell 59, 627–636 (1989).

    Article  CAS  Google Scholar 

  8. Hatakeyama, M. et al. Science 252, 1523–1528 (1991).

    Article  ADS  CAS  Google Scholar 

  9. Abraham, K. M. Levin, S. D., Marth, J. D., Forbush, K. A. &, Perlmutter, R. M. J. exp. Med. 173, 1421–1432 (1991).

    Article  CAS  Google Scholar 

  10. Reynolds, P. J. et al. Molec. cell. Biol. 10, 4266–4270 (1990).

    Article  CAS  Google Scholar 

  11. Veillette, A., Zu̇n̄iga-Pflücker, J. C., Bolen, J. B. & Kruisbeek, A. M. J. exp. Med 170, 1671–1680 (1989).

    Article  CAS  Google Scholar 

  12. Ferrick, D. A., Ohashi, P. S., Wallace, V., Schilham, M. & Mak, T. W. Immun. Today 10, 403–407 (1989).

    Article  CAS  Google Scholar 

  13. von Beohmer, H. A. Rev. Immun. 8, 531–556 (1990).

    Article  Google Scholar 

  14. Veillette, A., Bookman, M. A., Horak, E. M., Samelson, L. E. & Bolen, J. B. Nature 338, 257–259 (1989).

    Article  ADS  CAS  Google Scholar 

  15. Miceli, M. C., von Hoegen, P. & Parnes, J. R. Proc. natn. Acad. Sci. U.S.A. 88, 2623–2627 (1991).

    Article  ADS  CAS  Google Scholar 

  16. Abraham, N., Miceli, M. C., Parnes, J. R. & Veillette, A. Nature 350, 62–66 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Glaichenhaus, N., Shastri, N., Littman, D. R. & Turner, J. M. Cell 64, 511–520 (1991).

    Article  CAS  Google Scholar 

  18. June, C. H. et al. Proc. natn. Acad. Sci. U.S.A. 87, 7722–7726 (1990).

    Article  ADS  CAS  Google Scholar 

  19. Klausner, R. D. & Samelson, L. E. Cell 64, 875–878 (1991).

    Article  CAS  Google Scholar 

  20. Taylor, I. W. J. Histochem. Cytochem. 28, 1021–1024 (1980).

    Article  CAS  Google Scholar 

  21. Egerton, M., Scollay, R. & Shortman, K. Proc. natn. Acad. Sci. U.S.A. 87, 2579–2582 (1990).

    Article  ADS  CAS  Google Scholar 

  22. Cosgrove, D. et al. Cell 66, 1051–1066 (1991).

    Article  CAS  Google Scholar 

  23. Kühn, R., Rajewsky, K. & Müller, W. Science 254, 70V–710 (1991).

    Article  Google Scholar 

  24. Soriano, P., Montgomery, C. Geske, R. & Bradley, A. Cell 64, 693–702 (1991).

    Article  CAS  Google Scholar 

  25. Rahemtulla, A. et al. Nature 353, 180–184 (1991).

    Article  ADS  CAS  Google Scholar 

  26. Fung-Leung, W.-P. et al. Cell 65, 443–449 (1991).

    Article  CAS  Google Scholar 

  27. Huesmann, M., Scott, B., Kisielow, P. & von Boehmer, J. Cell 66, 533–540 (1991).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  29. Paige, C. J. & Skarvall, H. J. immunol. Meth. 52, 51–6L (1982).

    Article  CAS  Google Scholar 

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Author notes

  1. W. van Ewijk: Department of Cell Biology II and Immunology, Erasmus Universiteit, 3000 DR Rotterdam, The Netherlands

  2. K.-U. Hartmann: Institut für Experimented Immunologie, Philipps-Universität, D-3550 Marburg, Germany

  3. A. Veillette and D. Davidson: McGill Cancer Centre, McGill University, Montréal, Québec H3G 1Y6, Canada

  4. T. W. Mak: To whom correspondence should be addressed.

Authors and Affiliations

  1. Ontario Cancer Institute and Departments of Immunology and Medical Biophysics, University of Toronto, 500 Sherbourne Street, Toronto, Ontario, M4X1K9, Canada

    T. J. Molina, K. Kishihara, D. P. Siderovskid, W. van Ewijk, A. Narendran, E. Timms, A. Wakeham, C. J. Paige, K.-U. Hartmann, A. Veillette, D. Davidson & T. W. Mak

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  1. T. J. Molina
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  2. K. Kishihara
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  3. D. P. Siderovskid
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  6. E. Timms
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  7. A. Wakeham
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  10. A. Veillette
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Molina, T., Kishihara, K., Siderovskid, D. et al. Profound block in thymocyte development in mice lacking p56lck. Nature 357, 161–164 (1992). https://doi.org/10.1038/357161a0

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