Skip to main content
Log in

TheIL-4 andIL-5 genes are closely linked and are part of a cytokine gene cluster on mouse chromosome 11

  • Published:
Somatic Cell and Molecular Genetics

Abstract

The murine IL-4and IL-5genes encode hemopoietic growth factors involved in the stimulation, proliferation, and differentiation of cells of the T lymphocyte, B lymphocyte, and granulocyte lineages. We have mapped the Il-4 and Il-5 loci representing the structural genes for IL-4and IL-5,respectively, to mouse chromosome 11 using Chinese hamster ×mouse and rat × mouse somatic cell hybrids. Physical linkage studies of the IL-4and IL-5genes by pulsed field gel electrophoresis have shown that they are closely linked, being 110–180 kb apart. Since the Il-5 locus maps to the interface of bands A5 and B1 in the same location as the genes for IL-3and GM-CSF, this places these three cytokine genes, as well as the IL-4 gene, within a region of about 5000–10,000 kb. The present physical linkage studies indicate that the IL-4and IL-5genes are a minimum of 600 kb apart from the closely linked IL-3and GM-CSFgenes. The gene clustering, together with similarities in gene structure, regulation, and biological function, raises the possibility that the four genes may be part of a distantly related cytokine gene family.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Literature cited

  1. Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A., and Coffmann, R.L. (1986).J. Immunol. 136:2348–2357.

    PubMed  Google Scholar 

  2. Coffman, R.L., Shrader, B., Carty, J., Mosmann, T.R., and Bond, M.W. (1987).J. Immunol. 139:3685–3690.

    PubMed  Google Scholar 

  3. Noelle, R., Krammer, P.H., Ohara, J., Uhr, J.W., and Vitetta, E.S. (1984).Proc. Natl. Acad. Sci. U.S.A. 81:6149–6153.

    PubMed  Google Scholar 

  4. Roehm, N.W., Liebson, H.J., Zlotnick, A., Kappler, J., Marrack, P., and Cambier, J.C. (1984).J. Exp. Med. 160:679–694.

    PubMed  Google Scholar 

  5. Vitetta, E.S., Brooks, K., Chen, Y.W., Isakson, P., Jones, S., Layton, J., Mishra, G.C., Pure, E., Weiss, E., Ward, C., Yuan, D., Tucker, P., Uhr, J.W., and Krammer, P.H. (1984).Immunol. Rev. 78:137–157.

    PubMed  Google Scholar 

  6. Sideras, P., Bergstedt-Lindqvist, S., MacDonald, H.R., and Severinson, E. (1985).Eur. J. Immunol. 15:586–598.

    PubMed  Google Scholar 

  7. Vitetta, E.S., Ohara, J., Myers, C., Layton, J., Krammer, P., and Paul, W.E. (1985).J. Exp. Med. 162:1726–1731.

    PubMed  Google Scholar 

  8. Coffman, R.L., Ohara, J., Bond, M.W., Carty, J., Zlotnick, E., and Paul, W.E. (1986).J. Immunol. 136:4538–4541.

    PubMed  Google Scholar 

  9. Warren, D.J., and Sanderson, C.J. (1985).Immunology 54:615–623.

    PubMed  Google Scholar 

  10. Kinashi, T., Harada, N., Severinson, E., Tanabe, T., Sideras, P., Konishi, M., Azuma, C., Tominaga, A., Bergstedt-Lindqvist, S., Takahashi, M., Matsuda, F., Yaoita, Y., Takatsu, K., and Honjo, T. (1986).Nature 324:70–73.

    PubMed  Google Scholar 

  11. Yokota, T., Coffman, R.L., Hagiwara, H., Rennick, D.M., Takebe, Y., Yokota, K., Gemmell, L., Shrader, B., Yang, G., Meyerson, P., Luh, J., Hoy, P., Pene, J., Briere, F., Spits, H., Banchereau, J., de Vries, J., Lee, F.D., Aria, N., and Arai, K. (1987).Proc. Natl. Acad. Sci. U.S.A. 84:7388–7392.

    PubMed  Google Scholar 

  12. Metcalf, D. (1985).Science 229:16–22.

    PubMed  Google Scholar 

  13. Miyatake, S., Yokota, T., Lee, F., and Arai, K.-I. (1985).Proc. Natl. Acad. Sci. U.S.A. 82:318–320.

    Google Scholar 

  14. Miyatake, S., Otsuka, T., Yokota, T., Lee, F., and Arai, K. (1985).EMBO J. 4: 2561–2568.

    PubMed  Google Scholar 

  15. Campbell, H.D., Ymer, S., Fung, M.-C., and Young, I.G. (1985).Eur. J. Biochem. 150:297–304.

    PubMed  Google Scholar 

  16. Campbell, H.D., Sanderson, C.J., Wang, Y., Hort, Y., Martinson, M.E., Tucker, W.Q.J., Stellwagen, A., Strath, M., and Young, I.G. (1988).Eur. J. Biochem. 174:345–352.

    PubMed  Google Scholar 

  17. Stanley, E., Metcalf, D., Sobieszczuk, P., Gough, N.M., and Dunn, A.R. (1985).EMBO J. 4:2569–2573.

    PubMed  Google Scholar 

  18. Otsuka, T., Villaret, D., Yokota, T., Takebe, Y., Lee, F., Arai, N., and Arai, K.I. (1987).Nucleic Acids Res. 15:333–344.

    PubMed  Google Scholar 

  19. Sanderson, C.J., Campbell, H.D., and Young, I.G. (1988).Immunol. Rev. 102:29–50.

    PubMed  Google Scholar 

  20. Ralph, P., Broxmeyer, H.E., and Nakoinz, I. (1977).J. Exp. Med. 146:611–616.

    PubMed  Google Scholar 

  21. Hume, D.A., Summers, K.M., Cohen, D.R., and Allan, W. (1985).FEBS Lett. 180:271–274.

    PubMed  Google Scholar 

  22. Piacibello, W., Lu, L., Wachter, M., Rubin, B., and Broxmeyer, H.E. (1985).Blood 66:1343–1351.

    PubMed  Google Scholar 

  23. Metcalf, D. (1984).The Haemopoietic Colony Stimulating Factors (Elsevier, Amsterdam).

    Google Scholar 

  24. Broudy, V.C., Kaushansky, K., Segal, G.M., Harlan, J.N., and Adamson, J.W. (1986).Proc. Natl. Acad. Sci. U.S.A. 83:7467–7471.

    PubMed  Google Scholar 

  25. Munker, R., Gasson, J., Ogawa, M., and Koeffler, H.P. (1986).Nature 323:79–82.

    PubMed  Google Scholar 

  26. Brown, M.A., Pierce, J.H., Watson, C.J., Falco, J., Ihle, J.N., and Paul, W.E. (1987).Cell 50:809–818.

    PubMed  Google Scholar 

  27. Ihle, J.N., Silver, J., and Kozak, C.A. (1987).J. Immunol. 138:3051–3054.

    PubMed  Google Scholar 

  28. Barlow, D.P., Bucan, M., Lehrach, H., Hogan, B.L.M., and Gough, N.M. (1987).EMBO J. 6:617–623.

    PubMed  Google Scholar 

  29. Gough, N.M., Gough, J., Metcalf, D., Kelso, A., Grail, D., Nicola, N.A., Burgess, A.W., and Dunn, A.R. (1984).Nature 309:763–767.

    PubMed  Google Scholar 

  30. Lee, F., Yokota, T., Otsuka, T., Meyerson, P., Villaret, D., Coffman, R., Mosmann, T., Rennick, D., Roehm, N., Smith, C., Zlotnik, A., and Arai, K.I. (1986).Proc. Natl. Acad. Sci. U.S.A. 83:2061–2065.

    PubMed  Google Scholar 

  31. Feinberg, A.P., and Vogelstein, B. (1983).Anal. Biochem. 132:6–13.

    PubMed  Google Scholar 

  32. Kozak, C.A., and Rowe, W.P. (1979).Science 204:69–71.

    PubMed  Google Scholar 

  33. Watson, D.K., McWilliams-Smith, M.J., Kozak, C., Reeves, R., Gearhart, J., Nunn, M.F., Nash, W., Fowle, J.R., III, Duesberg, P., Papas, T.S., and O'Brien, S.J. (1986).Proc. Natl. Acad. Sci. U.S.A. 83:1792–1796.

    PubMed  Google Scholar 

  34. Killary, A.M., and Fournier, R.E.K. (1984).Cell 38:523–524.

    PubMed  Google Scholar 

  35. Maniatis, T., Fritsch, E.F., and Sambrook, J. (1982). Molecular cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York).

    Google Scholar 

  36. Jackson, D.A., and Cook, P.R. (1985).EMBO J. 4:913–918.

    PubMed  Google Scholar 

  37. Overhauser, J., and Radic, M.Z. (1987).BRL Focus 9:(3):8–9.

    Google Scholar 

  38. Carle, G.F., Frank, M., and Olson, M.V. (1986).Science 232:65–68.

    PubMed  Google Scholar 

  39. Schwartz, D.C., and Cantor, C.R. (1984).Cell 37:67–75.

    PubMed  Google Scholar 

  40. Chu, G., Vollrath, D., and Davis, R.W. (1986).Science 234:1582–1585.

    PubMed  Google Scholar 

  41. Herrmann, B.G., Barlow, D.P., and Lehrach, H. (1987).Cell 48:813–825.

    PubMed  Google Scholar 

  42. Bostock, C.J. (1988).Nucleic Acids Res. 16:4239–4252.

    PubMed  Google Scholar 

  43. Gardiner, K., Laas, W., and Patterson, D. (1986).Somat. Cell Mol. Genet. 12:185–195.

    PubMed  Google Scholar 

  44. Gardiner, K., and Patterson, D. (1988).Nature 331:371–372.

    Google Scholar 

  45. Carle, G.F., and Olson, M.V. (1984).Nucleic Acids Res. 12:5647–5664.

    PubMed  Google Scholar 

  46. Orbach, M.J., Vollrath, D., Davis, R.W., and Yanofsky, C. (1988).Mol. Cell. Biol. 8:1469–1473.

    PubMed  Google Scholar 

  47. Fung, M.C., Hapel, A.J., Ymer, S., Cohen, D.R., Johnson, R.M., Campbell, H.D., and Young, I.G. (1984).Nature 307:233–237.

    Google Scholar 

  48. Yokota, T., Lee, F., Rennick, D., Hall, C. Arai, N., Mosmann, T., Nabel, G., Cantor, H., and Arai, K.-I. (1984).Proc. Natl. Acad. Sci. U.S.A. 81:1070–1074.

    PubMed  Google Scholar 

  49. Yang, Y.-C., Ciarletta, A.B., Temple, P.A., Chung, M.P., Kovacic, S., Witek-Giannotti, J.S., Leary, A.C., Kriz, R., Donahue, R.E., Wong, G.G., and Clark, S.C. (1986).Cell 47:3–10.

    PubMed  Google Scholar 

  50. Wong, G.G., Witek, J.S., Temple, P.A., Wolkens, K.M., Leary, A.C., Luxenberg, D.P., Jones, S.S., Brown, E.L., Kay, R.M., Orr, E.C., Shoemaker, C., Golde, D.W., Kaufman, R.J., Hewick, R.M., Wang, E.A., and Clark, S.C. (1985).Science 228:810–815.

    PubMed  Google Scholar 

  51. Noma, Y., Sideras, P., Naito, T., Bergstedt-Lindquist, S., Azuma, C. Severinson, E., Tanabe, T., Kinashi, T., Matsuda, F., Yaoita, Y., and Honjo, T. (1986).Nature 319:640–646.

    PubMed  Google Scholar 

  52. Campbell, H.D., Tucker, W.Q.J., Hort, Y., Martinson, M.E., Mayo, G., Clutterbuck, E.J., Sanderson, C.J., and Young, I.G. (1987).Proc. Natl. Acad. Sci. U.S.A. 84:6629–6633.

    Google Scholar 

  53. Azuma, C., Tanabe, T., Konishi, M., Kinashi, T., Noma, T., Matsuda, F., Yaoita, Y., Takatsu, K., Hammarstrom, L., Smith, C.I.E., Severinson, E., and Honjo, T. (1986).Nucleic Acids Res. 14:9149–9158.

    PubMed  Google Scholar 

  54. Tanabe, T., Konishi, M., Mizuta, T., Noma, T., and Honjo, T. (1987).J. Biol. Chem. 262:16580–16584.

    PubMed  Google Scholar 

  55. Naylor, S.L., Sakaguchi, A.Y., Shows, T.B., Law, M.L., Goeddel, D.V., and Gray, P.W. (1983).J. Exp. Med. 57:1020–1027.

    Google Scholar 

  56. Seigel, L.J., Harper, M.E., Wong-Staal, F., Gallo, R.C., Nash, W.G., and O'Brien, S.J. (1984).Science 223:175–178.

    PubMed  Google Scholar 

  57. Naylor, S.L., Gray, P.W., and Lalley, P.A. (1984)Somat. Cell Mol. Genet. 10:531–534.

    PubMed  Google Scholar 

  58. Allen, N.D., Cran, D.G., Barton, S.C., Hettle, S., Reik, W., and Azim, Surani, M. (1988).Nature 333:852–855.

    Google Scholar 

  59. Forrester, W.C., Takegawa, S., Papayannopoulou, T., Stamatoyannopoulos, G., and Groudine, M. (1987).Nucleic Acids Res. 15:10159–10177.

    PubMed  Google Scholar 

  60. Grosveld, F., Blom van Assendelft, G., Greaves, D.R., and Kollias, G. (1987).Cell 51:975–985.

    PubMed  Google Scholar 

  61. Huebner, K., Isobe, M., Croce, C.M., Golde, D.W., Kaufman, S.E., and Gasson, J.C. (1985).Science 230:1282–1285.

    PubMed  Google Scholar 

  62. Le Beau, M.M., Epstein, N.D., O'Brien, S.J., Nienhuis, A.W., Yang, Y.-C., Clark, S.C., and Rowley, J.D. (1987).Proc. Natl. Acad. Sci. U.S.A. 84:5913–5917.

    PubMed  Google Scholar 

  63. Sutherland, G.R., Baker, E., Callen, D.F., Campbell, H.D., Young, I.G., Sanderson, C.J., Garson, O.M., Lopez, A.F., and Vadas, M.A. (1988).Blood 71:1150–1152.

    PubMed  Google Scholar 

  64. Yang, Y.-C., Kovacic, S., Kriz, R., Wolf, S., Clark, S.C., Wellems, T.E., Nienhuis, A., and Epstein, N. (1988).Blood 71:958–961.

    PubMed  Google Scholar 

  65. Van den Berghe, H., Vermaelen, K., Mecucci, C., Barbieri, D., and Tricot, G. (1985).Cancer Genet. Cytogenet. 17:189–255.

    PubMed  Google Scholar 

  66. Morgan, R., Walter, T.A., Decker, H.J., Hecht, F., and Sandberg, A.A. (1988).Cancer Genet. Cytogenet. 32:267–275.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, J.S., Campbell, H.D., Kozak, C.A. et al. TheIL-4 andIL-5 genes are closely linked and are part of a cytokine gene cluster on mouse chromosome 11. Somat Cell Mol Genet 15, 143–152 (1989). https://doi.org/10.1007/BF01535075

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01535075

Keywords

Navigation