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Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted State6 gene

Abstract

SIGNAL transducers and activators of transcription (Stats) are activated by tyrosine phosphorylation in response to cytokines, and are thought to mediate many of their functional responses1–4. Stat6 is activated in response to interleukin (IL)-4 (refs 5,6) and may contribute to various functions including mitogenesis, T-helper cell differentiation and immunoglobulin i so type switching7. To evaluate the role of Stat6, we generated Stat6-null mice (Stat6-l-) by gene disruption in embryonic stem cells. The mice were viable, indicating the lack of a non-redundant function in normal development. Although naive lymphoid cell development was normal, Stat6-l- mice were deficient in IL-4-mediated functions including Th2 helper T-cell differentiation, expression of cell surface markers, and immunoglobulin class switching to IgE. In contrast, IL-4-mediated proliferation was only partly affected.

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References

  1. 1

    Ihle, J. N. Nature 377, 591–594 (1995).

  2. 2

    Ihle, J. N. Cell 84, 331–334 (1996).

  3. 3

    Schindler, C. & Darnell, J. E. Jr A Rev. Biochem. 64, 621–651 (1995).

  4. 4

    Darnell, J. E. Jr, Kerr, I. M. & Stark, G. M. Science 264, 1415–1421 (1994).

  5. 5

    Hour, J. et al. Science 265, 1701–1706 (1994).

  6. 6

    Quelle, F. W. et al. Molec. cell. Biol. 15, 3336–3343 (1995).

  7. 7

    Paul, W. E. & Seder, R. A. Cell 76, 241–251 (1994).

  8. 8

    Snapper, C. M., Hornbeck, P. V., Atasoy, U., Pereira, G. M. & Paul, W. E. Proc. natn. Acad. Sci. U.S.A. 85, 6107–6110 (1988).

  9. 9

    Le-Gros, G., Ben-Sasson, S. Z., Seder, R., Finkelman, F. D. & Paul, W. E. J. exp. Med. 172, 921–929 (1990).

  10. 10

    Swain, S. L., Weinberg, A. D., English, B. & Huston, G. J. Immun. 145, 3796–3806 (1990).

  11. 11

    Kühn, R., Rajewsky, K. & Müller, W. Science 254, 707–710 (1991).

  12. 12

    Coffman, R. L. et al. J. Immun. 136, 4538–4541 (1996).

  13. 13

    Katona, I. M., Urban, J. F. Jr, Kang, S. S., Paul, W. E. & Finkelman, F. D. J. Immun. 146, 4215–4221 (1991).

  14. 14

    Ryan, J. J. et al. Immunity 4, 123–132 (1996).

  15. 15

    Wang, H. Y., Paul, W. E. & Keegan, A. Immunity 4 113–122 (1996).

  16. 16

    Kretsovali, A. & Papamatheakis, J. Nucleic Acids Res. 23, 2919–2928 (1995).

  17. 17

    Kohler, I. & Rieber, E. P. Eur. J. Immun. 23, 3066–3071 (1993).

  18. 18

    Kotanides, H. & Reich, N. C. Science 262, 1265–1267 (1993).

  19. 19

    Richards, M. L. & Katz, D. H. J. Immun. 22, 3453–3466 (1994).

  20. 20

    Seder, R. A. & Paul, W. E. A. Rev. Immun. 12, 635–673 (1994).

  21. 21

    Kopf, M. et al. Nature 362, 245–248 (1993).

  22. 22

    Jacobson, N. G. et al. J. exp. Med. 181(5), 1755–1762 (1995).

  23. 23

    Coffman, R. L., Lebman, D. A. & Rothman, P. Adv. Immun. 54, 229–270 (1993).

  24. 24

    Schindler, C., Kashleva, H., Pernis, A., Pine, R. & Rothman, P. EMBO J. 13, 1350–1356 (1994).

  25. 25

    Lin, J.-X. et al. Immunity 2, 331–339 (1995).

  26. 26

    Meraz, M. A. et al. Cell 84, 431–442 (1996).

  27. 27

    Durbin, J. E., Hackenmiller, R., Simon, M. C. & Levy, D. E. Cell 84, 443–450 (1996).

  28. 28

    Nosaka, T. et al. Science 270, 800–802 (1995).

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