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Somatic Cell and Molecular Genetics

, Volume 15, Issue 2, pp 143–152 | Cite as

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

  • Janet S. Lee
  • Hugh D. Campbell
  • Christine A. Kozak
  • Ian G. Young
Article

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.

Keywords

Gene Family Gene Cluster Biological Function Somatic Cell Gene Structure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Literature cited

  1. 1.
    Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A., and Coffmann, R.L. (1986).J. Immunol. 136:2348–2357.PubMedGoogle Scholar
  2. 2.
    Coffman, R.L., Shrader, B., Carty, J., Mosmann, T.R., and Bond, M.W. (1987).J. Immunol. 139:3685–3690.PubMedGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 4.
    Roehm, N.W., Liebson, H.J., Zlotnick, A., Kappler, J., Marrack, P., and Cambier, J.C. (1984).J. Exp. Med. 160:679–694.PubMedGoogle Scholar
  5. 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.PubMedGoogle Scholar
  6. 6.
    Sideras, P., Bergstedt-Lindqvist, S., MacDonald, H.R., and Severinson, E. (1985).Eur. J. Immunol. 15:586–598.PubMedGoogle Scholar
  7. 7.
    Vitetta, E.S., Ohara, J., Myers, C., Layton, J., Krammer, P., and Paul, W.E. (1985).J. Exp. Med. 162:1726–1731.PubMedGoogle Scholar
  8. 8.
    Coffman, R.L., Ohara, J., Bond, M.W., Carty, J., Zlotnick, E., and Paul, W.E. (1986).J. Immunol. 136:4538–4541.PubMedGoogle Scholar
  9. 9.
    Warren, D.J., and Sanderson, C.J. (1985).Immunology 54:615–623.PubMedGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 12.
    Metcalf, D. (1985).Science 229:16–22.PubMedGoogle Scholar
  13. 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. 14.
    Miyatake, S., Otsuka, T., Yokota, T., Lee, F., and Arai, K. (1985).EMBO J. 4: 2561–2568.PubMedGoogle Scholar
  15. 15.
    Campbell, H.D., Ymer, S., Fung, M.-C., and Young, I.G. (1985).Eur. J. Biochem. 150:297–304.PubMedGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 17.
    Stanley, E., Metcalf, D., Sobieszczuk, P., Gough, N.M., and Dunn, A.R. (1985).EMBO J. 4:2569–2573.PubMedGoogle Scholar
  18. 18.
    Otsuka, T., Villaret, D., Yokota, T., Takebe, Y., Lee, F., Arai, N., and Arai, K.I. (1987).Nucleic Acids Res. 15:333–344.PubMedGoogle Scholar
  19. 19.
    Sanderson, C.J., Campbell, H.D., and Young, I.G. (1988).Immunol. Rev. 102:29–50.PubMedGoogle Scholar
  20. 20.
    Ralph, P., Broxmeyer, H.E., and Nakoinz, I. (1977).J. Exp. Med. 146:611–616.PubMedGoogle Scholar
  21. 21.
    Hume, D.A., Summers, K.M., Cohen, D.R., and Allan, W. (1985).FEBS Lett. 180:271–274.PubMedGoogle Scholar
  22. 22.
    Piacibello, W., Lu, L., Wachter, M., Rubin, B., and Broxmeyer, H.E. (1985).Blood 66:1343–1351.PubMedGoogle Scholar
  23. 23.
    Metcalf, D. (1984).The Haemopoietic Colony Stimulating Factors (Elsevier, Amsterdam).Google Scholar
  24. 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.PubMedGoogle Scholar
  25. 25.
    Munker, R., Gasson, J., Ogawa, M., and Koeffler, H.P. (1986).Nature 323:79–82.PubMedGoogle Scholar
  26. 26.
    Brown, M.A., Pierce, J.H., Watson, C.J., Falco, J., Ihle, J.N., and Paul, W.E. (1987).Cell 50:809–818.PubMedGoogle Scholar
  27. 27.
    Ihle, J.N., Silver, J., and Kozak, C.A. (1987).J. Immunol. 138:3051–3054.PubMedGoogle Scholar
  28. 28.
    Barlow, D.P., Bucan, M., Lehrach, H., Hogan, B.L.M., and Gough, N.M. (1987).EMBO J. 6:617–623.PubMedGoogle Scholar
  29. 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.PubMedGoogle Scholar
  30. 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.PubMedGoogle Scholar
  31. 31.
    Feinberg, A.P., and Vogelstein, B. (1983).Anal. Biochem. 132:6–13.PubMedGoogle Scholar
  32. 32.
    Kozak, C.A., and Rowe, W.P. (1979).Science 204:69–71.PubMedGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. 34.
    Killary, A.M., and Fournier, R.E.K. (1984).Cell 38:523–524.PubMedGoogle Scholar
  35. 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. 36.
    Jackson, D.A., and Cook, P.R. (1985).EMBO J. 4:913–918.PubMedGoogle Scholar
  37. 37.
    Overhauser, J., and Radic, M.Z. (1987).BRL Focus 9:(3):8–9.Google Scholar
  38. 38.
    Carle, G.F., Frank, M., and Olson, M.V. (1986).Science 232:65–68.PubMedGoogle Scholar
  39. 39.
    Schwartz, D.C., and Cantor, C.R. (1984).Cell 37:67–75.PubMedGoogle Scholar
  40. 40.
    Chu, G., Vollrath, D., and Davis, R.W. (1986).Science 234:1582–1585.PubMedGoogle Scholar
  41. 41.
    Herrmann, B.G., Barlow, D.P., and Lehrach, H. (1987).Cell 48:813–825.PubMedGoogle Scholar
  42. 42.
    Bostock, C.J. (1988).Nucleic Acids Res. 16:4239–4252.PubMedGoogle Scholar
  43. 43.
    Gardiner, K., Laas, W., and Patterson, D. (1986).Somat. Cell Mol. Genet. 12:185–195.PubMedGoogle Scholar
  44. 44.
    Gardiner, K., and Patterson, D. (1988).Nature 331:371–372.Google Scholar
  45. 45.
    Carle, G.F., and Olson, M.V. (1984).Nucleic Acids Res. 12:5647–5664.PubMedGoogle Scholar
  46. 46.
    Orbach, M.J., Vollrath, D., Davis, R.W., and Yanofsky, C. (1988).Mol. Cell. Biol. 8:1469–1473.PubMedGoogle Scholar
  47. 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. 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.PubMedGoogle Scholar
  49. 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.PubMedGoogle Scholar
  50. 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.PubMedGoogle Scholar
  51. 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.PubMedGoogle Scholar
  52. 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. 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.PubMedGoogle Scholar
  54. 54.
    Tanabe, T., Konishi, M., Mizuta, T., Noma, T., and Honjo, T. (1987).J. Biol. Chem. 262:16580–16584.PubMedGoogle Scholar
  55. 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. 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.PubMedGoogle Scholar
  57. 57.
    Naylor, S.L., Gray, P.W., and Lalley, P.A. (1984)Somat. Cell Mol. Genet. 10:531–534.PubMedGoogle Scholar
  58. 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. 59.
    Forrester, W.C., Takegawa, S., Papayannopoulou, T., Stamatoyannopoulos, G., and Groudine, M. (1987).Nucleic Acids Res. 15:10159–10177.PubMedGoogle Scholar
  60. 60.
    Grosveld, F., Blom van Assendelft, G., Greaves, D.R., and Kollias, G. (1987).Cell 51:975–985.PubMedGoogle Scholar
  61. 61.
    Huebner, K., Isobe, M., Croce, C.M., Golde, D.W., Kaufman, S.E., and Gasson, J.C. (1985).Science 230:1282–1285.PubMedGoogle Scholar
  62. 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.PubMedGoogle Scholar
  63. 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.PubMedGoogle Scholar
  64. 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.PubMedGoogle Scholar
  65. 65.
    Van den Berghe, H., Vermaelen, K., Mecucci, C., Barbieri, D., and Tricot, G. (1985).Cancer Genet. Cytogenet. 17:189–255.PubMedGoogle Scholar
  66. 66.
    Morgan, R., Walter, T.A., Decker, H.J., Hecht, F., and Sandberg, A.A. (1988).Cancer Genet. Cytogenet. 32:267–275.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Janet S. Lee
    • 1
  • Hugh D. Campbell
    • 1
  • Christine A. Kozak
    • 2
  • Ian G. Young
    • 1
  1. 1.Medical Molecular Biology, John Curtin School of Medical ResearchAustralian National UniversityCanberraAustralia
  2. 2.Laboratory of Viral DiseasesNational Institute of Allergy and Infectious Diseases, National Cancer InstituteBethesda

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