Phenotypes of TGFß Knockout Mice

  • Suhas Kallapur
  • Marcia Shull
  • Thomas Doetschman
Part of the Contemporary Immunology book series (CONTIM)


The transforming growth factor-ß (TGFß) family consists of structurally related polypeptides that mediate important physiological processes. Significant advances have been made recently in understanding the functions of these molecules in vivo by the targeted ablation of various members of the super gene family. The family members include the TGF(is, activins, inhibins, bone morphogenetic proteins, Müllerian-inhibiting substance, nodal, dorsalin,and the products of the Drosophila decapentaplegic, and Xenopus Vg-1 genes (for review see refs. 1–4). Recently, the growth differentiation factor (GDF) family of proteins, a new member of the TGFβ family, has been described (5–7). TGFβl was first isolated from human platelets (8) and the cDNA sequence was later determined (9). TGFß 1 is a disulfide-linked homo-dimer of two 112 amino acid chains. Each chain is synthesized as the C-terminal domain of a 390 amino acid precursor. It has the characteristics of a secretory polypeptide, contains a hydrophobic signal sequence for translocation across the endoplasmic reticulum, and is glycosylated. The precursor cleavage site is a sequence of four basic amino acids immediately preceding the bioactive domain (9).


Transform Growth Factor Granulosa Cell Kawasaki Disease Null Mouse Transform Growth Factor Beta 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Massague, J. (1990) The transforming growth factor-beta family. Ann. Rev. Cell Biol. 6, 597 - 641.PubMedCrossRefGoogle Scholar
  2. 2.
    Kingsley, D. M. (1994) The TGF-beta superfamily. new members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 8, 133 - 146.PubMedCrossRefGoogle Scholar
  3. 3.
    Roberts, A. B. and Sporn, M. B. (1988) Transforming growth factor beta. Adv. Cancer Res. 51, 107 - 145.PubMedCrossRefGoogle Scholar
  4. 4.
    Barnard, J. A., Lyons, R. M., and Moses, H. L. (1990) The cell biology of transforming growth factor beta. Biochim. Biophys. Acta 1032, 79 - 87.Google Scholar
  5. 5.
    Storm, E. E., Huynh, T. V., Copeland, N. G., Jenkins, N. A., Kingsley, D. M., and Lee, S. J. (1994) Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily. Nature 368, 639 - 643.PubMedCrossRefGoogle Scholar
  6. 6.
    McPherron, A. C. and Lee, S. J. (1993) GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines. J. Biol. Chem. 268, 3444 - 3449.PubMedGoogle Scholar
  7. 7.
    Lee, S. J. (1991) Expression of growth/differentiation factor 1 in the nervous system: conservation of a bicistronic structure. Proc. Nat. Acad. Sci. USA 88, 4250 - 4254.PubMedCrossRefGoogle Scholar
  8. 8.
    Assoian, R. K., Komoriya, A., Meyers, C. A., Miller, D. M., and Sporn, M. B. (1983) Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J. Biol. Chem. 258, 7155 - 7160.PubMedGoogle Scholar
  9. 9.
    Derynck, R., Jarrett, J. A., Chen, E. Y., Eaton, D. H., Bell, J. R., Assoian, R. K., Roberts, A. B., Sporn, M. B., and Goeddel, D. V. (1985) Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature 316, 701 - 705.PubMedCrossRefGoogle Scholar
  10. 10.
    Wrana, J. L., Attisano, L., Wieser, R., Ventura, F., and Massague, J. (1994) Mechanism of activation of the TGF-beta receptor. Nature 370, 341 - 347.PubMedCrossRefGoogle Scholar
  11. 11.
    Lopez-Casillas, F., Payne, H. M., Andres, J. L., and Massague, J. (1994) Betaglycan can act as a dual modulator of TGF-beta access to signaling receptors: mapping of ligand binding and GAG attachment sites. J. Cell Biol. 124, 557 - 568.PubMedCrossRefGoogle Scholar
  12. 12.
    Lopez-Casillas, F., Cheifetz, S., Doody, J., Andres, J. L., Lane, W. S., and Massague, J. (1991) Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system. Cell 67, 785 - 795.PubMedCrossRefGoogle Scholar
  13. 13.
    Shull, M. M. and Doetschman, T. (1994) Transforming growth factor-beta 1 in reproduction and development. Mol. Reprod. Dey. 39, 239 - 246.CrossRefGoogle Scholar
  14. 14.
    Wall, N. A. and Hogan, B. L. (1994) TGF-beta related genes in development. Curr. Opinion Genetics Dev. 4, 517 - 522.CrossRefGoogle Scholar
  15. 15.
    Hoffmann, F. M. (1991) Transforming growth factor-beta-related genes in Drosophila and vertebrate development. Curr. Opinion Cell Biol. 3, 947 - 952.PubMedCrossRefGoogle Scholar
  16. 16.
    Wahl, S. M. (1992) Transforming growth factor beta (TGF-beta) in inflammation: a cause and a cure. J. Clin. Immunol. 12, 61 - 74.PubMedCrossRefGoogle Scholar
  17. 17.
    Ruscetti, F. W. and Palladino, M. A. (1991;) Transforming growth factor-beta and the immune system. Prog. Growth Factor Res. 3, 159 - 175.Google Scholar
  18. 18.
    Bonewald, L. F. and Dallas, S. L. (1994) Role of active and latent transforming growth factor beta in bone formation. J. Cell. Biochem. 55, 350 - 357.PubMedCrossRefGoogle Scholar
  19. 19.
    Centrella, M., Horowitz, M. C., Wozney, J. M., and McCarthy, T. L. (1994) Transforming growth factor-beta gene family members and bone. Endocrine Rev. 15, 27 - 39.Google Scholar
  20. 20.
    Centrella, M., McCarthy, T. L., and Canalis, E. (1989) Effects of transforming growth factors on bone cells. Connect. Tissue Res. 20, 267 - 275.CrossRefGoogle Scholar
  21. 21.
    Keller, J. R., Mcniece, I. K., Sill, K. T., Ellingsworth, L. R., Quesenberry, P. J., Sing, G. K., and Ruscetti, F. W. (1990) Transforming growth factor beta directly regulates primitive murine hematopoietic cell proliferation. Blood 75, 596 - 602.PubMedGoogle Scholar
  22. 22.
    Keller, J. R., Mantel, C., Sing, G. K., Ellingsworth, L. R., Ruscetti, S. K., and Ruscetti, F. W. (1988) Transforming growth factor beta 1 selectively regulates early murine hematopoietic progenitors and inhibits the growth of IL-3-dependent myeloid leukemia cell lines. J. Exp. Med. 168, 737 - 750.PubMedCrossRefGoogle Scholar
  23. 23.
    RayChaudhury, A. and D’ Amore, P. A. (1991) Endothelial cell regulation by transforming growth factor-beta. J. Cell. Biochem. 47, 224 - 229.CrossRefGoogle Scholar
  24. 24.
    Roberts, A. B., Sporn, M. B., Assoian, R. K., Smith, J. M., Roche, N. S., Wakefield, L. M., Heine, U. I., Liotta, L. A., Falanga, V., Kehrl, J. H., et al. (1986) Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc. Nat. Acad. Sci. USA 83, 4167 - 4171.PubMedCrossRefGoogle Scholar
  25. 25.
    Sporn, M. B. and Roberts, A. B. (1986) Peptide growth factors and inflammation, tissue repair, and cancer. J. Clin. Invest. 78, 329 - 332.PubMedCrossRefGoogle Scholar
  26. 26.
    Roberts, A. B., Flanders, K. C., Heine, U. I., Jakowlew, S., Kondaiah, P., Kim, S. J., and Sporn, M. B. (1990) Transforming growth factor-beta: multi-functional regulator of differentiation and development. Philos. Trans. R. Soc. London—Series B: Biol. Sci. 327, 145 - 154.CrossRefGoogle Scholar
  27. 27.
    Roberts, A. B., Heine, U. I., Flanders, K. C., and Sporn, M. B. (1990) Transforming growth factor-beta. Major role in regulation of extracellular matrix. Ann. N. P. Acad. Sci. 580, 225 - 232.CrossRefGoogle Scholar
  28. 28.
    Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., Allen, R., Sidman, C., Proetzel, G., Calvin, D., Annunziata, N., and Doetschman, T. (1992) Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359, 693 - 699.Google Scholar
  29. 29.
    Proetzel, G., Pawlowski, S. A., Wiles, M. V., Yin, M., Boivin, G. P., Howles, P., Ding, J., Ferguson, M. W. J., and Doetschman, T. (1995) Transforming growth factor-133 is required for secondary palate fusion. Nature Genetics 11, 409 - 414.PubMedCrossRefGoogle Scholar
  30. 30.
    Kulkarni, A. B., Huh, C. G., Becker, D., Geiser, A., Lyght, M., Flanders, K. C., Roberts, A. B., Sporn, M. B., Ward, J. M., and Karlsson, S. (1993) Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Nat. Acad. Sci. USA 90, 770 - 774.CrossRefGoogle Scholar
  31. 31.
    Kaartinen, V., Voncken, J. W., Shuler, C., Warburton, D., Heisterkamp, N., and Groffen, J. (1995) Abnormal lung development and cleft palate: Defects of epithelial-mesenchymal interaction in mice lacking TGF-03. Nature Genetics 11, 415 - 421.Google Scholar
  32. 32.
    Hines, K. L., Kulkarni, A. B., McCarthy, J. B., Tian, H., Ward, J. M., Christ, M., McCartney-Francis, N. L., Furcht, L. T., Karlsson, S., and Wahl, S. M. (1994) Synthetic fibronectin peptides interrupt inflammatory cell infiltration in transforming growth factor beta 1 knockout mice. Proc. Nat. Acad. Sci. USA 91, 5187 - 5191.PubMedCrossRefGoogle Scholar
  33. 33.
    Diebold, R. J., Eis, M. J., Yin, M., Ormsby, I., Boivin, G. P., Darrow, B. J., Saffitz, J. E., and Doetschman, T. C. (1995) Early onset multifocal inflammation in the TGFB1-null mouse is lymphocyte mediated. Proc. Nat. Acad. Sci. USA 92, 12215 - 12219.PubMedCrossRefGoogle Scholar
  34. 34.
    Geiser, A. G., Letterio, J. J., Kulkarni, A. B., Karlsson, S., Roberts, A. B., and Sporn, M. B. (1993) Transforming growth factor beta 1 (TGF-beta 1) controls expression of major histocompatibility genes in the postnatal mouse: aberrant histocompatibility antigen expression in the pathogenesis of the TGF-beta 1 null mouse phenotype. Proc. Nat. Acad. Sci. USA 90, 9944 —9948.Google Scholar
  35. 35.
    Dang, H., Geiser, A. G., Letterio, J. L., Nakabayashi, T., Kong, L., Fernandes, G., and Talal, N. (1995) SLE-like autoantibodies and Sjogren’s syndrome-like lymphoproliferation in TGF-ß knock out mice. J. Immunol. 155, 3205 - 3212.PubMedGoogle Scholar
  36. 36.
    Christ, M., McCartney-Francis, N. L., Kulkarni, A. B., Ward, J. M., Mizel, D. E., Mackall, C. L., Gress, R. E., Hines, K. L., Tian, H., Karlsson, S., et al. (1994) Immune dysregulation in TGF-beta 1-deficient mice. J. Immunol. 153, 1936 - 1946.PubMedGoogle Scholar
  37. 37.
    Boivin, G. P., O’Toole, B. A., Orsmby, I. E., Diebold, R. J., Eis, M. J., Doetschman, T., and Kier, A. B. (1995) Onset and progression of pathological lesions in transforming growth factor-beta 1-deficient mice. Am. J. Pathol. 146, 276 - 288.PubMedGoogle Scholar
  38. 38.
    Dickson, M. C., Martin, J. S., Cousins, F. M., Kulkarni, A. B., Karlsson, S., and Akhurst, R. J. (1995) Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 121, 1845 - 1854.PubMedGoogle Scholar
  39. 39.
    Shull, M. M., Diebold, R., Eis, M., Boivin, G., Grupp, I. L., and Doetschman, T. (1995) Homologous recombination and growth factors, in Molecular Genetics and Gene Therapy of Cardiovascular Diseases. (Mockrin. S. C. ed.) Dekker, New York, pp. 371 - 401.Google Scholar
  40. 40.
    Shull, M. M., Kier, A. B., Diebold, R. J., Yin, M., and Doetschman, T. (1994) The importance of transforming growth factor 131 in immunological homeostasis as revealed by gene ablation in mice, in Overexpression and Knockout of Cytokines in Transgenic Mice. ( Jacon, C. ed.), Academic, Chicago, pp. 135 - 159.Google Scholar
  41. 41.
    Brown, R. L., Ormsby, I. O., Doetschman, T. C., and Greenhalgh, D. G. (1995) Wound healing in the transforming growth factor-131—deficient mouse. Wound Repair Regeneration 3, 25 - 36.CrossRefGoogle Scholar
  42. 42.
    Guenard, V., Rosenbaum, T., Gwynn, L. A., Doetschman, T., Ratner, N., and Wood, P. M. (1995) Effect of transforming growth factor-beta 1 and -beta 2 on Schwann cell proliferation on neurites. GLIA 13, 309 - 318.Google Scholar
  43. 43.
    Wahl, S. M. (1994) Transforming growth factor beta: the good, the bad, and the ugly. J. Exp. Med. 180, 1587 - 1590.PubMedCrossRefGoogle Scholar
  44. 44.
    Sasaki, H., Pollard, R. B., Schmitt, D., and Suzuki, F. (1992) Transforming growth factor-beta in the regulation of the immune response. Clin. Immunol. Immunopath. 65, 1 - 9.CrossRefGoogle Scholar
  45. 45.
    Kehrl, J. H., Taylor, A., Kim, S. J., and Fauci, A. S. (1991) Transforming growth factor-beta is a potent negative regulator of human lymphocytes. Ann. N. Y. Acad. Sci. 628, 345 - 353.Google Scholar
  46. 46.
    Roberts, A. B. and Sporn, M. B. (1990) The transforming growth factor-betas, in: Peptide Growth Factor and Their Receptors. ( Sporn, M. B. and Roberts, A. B., eds.), Springer-Verlag, Berlin, pp. 419 - 472.CrossRefGoogle Scholar
  47. 47.
    Reibman, J., Meixler, S., Lee, T. C., Gold, L. I., Cronstein, B. N., Haines,K. A., Kolasinski, S. L., and Weissmann, G. (1991) Transforming growth factor beta 1, a potent chemoattractant for human neutrophils, bypasses clas- sic signal-transduction pathways. Proc. Nat. Acad. Sci. USA 88, 6805 - 6809.Google Scholar
  48. 48.
    Wahl, S. M., Hunt, D. A., Wakefield, L. M., McCartney-Francis, N., Wahl,L. M., Roberts, A. B., and Sporn, M. B. (1987) Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc. Nat. Acad. Sci. USA 84, 5788 - 5792.Google Scholar
  49. 49.
    Gruber, B. L., Marchese, M. J., and Kew, R. R. (1994) Transforming growth factor-beta 1 mediates mast cell chemotaxis. J. Immunol. 152, 5860 - 5867.PubMedGoogle Scholar
  50. 50.
    Adams, D. H., Hathaway, M., Shaw, J., Burnett, D., Elias, E., and Strain, A. J. (1991) Transforming growth factor-beta induces human T lymphocyte migration in vitro. J. Immunol. 147, 609-612.Google Scholar
  51. 51.
    Parekh, T., Saxena, B., Reibman, J., Cronstein, B. N., and Gold, L. I. (1994) Neutrophil chemotaxis in response to TGF-beta isoforms (TGF-beta 1, TGF-beta 2, TGF-beta 3) is mediated by fibronectin. J. Immunol. 152, 2456 - 2466.PubMedGoogle Scholar
  52. 52.
    Chantry, D., Turner, M., Abney, E., and Feldmann, M. (1989) Modulation of cytokine production by transforming growth factor-beta. J. Immunol. 142, 4295 - 4300.PubMedGoogle Scholar
  53. 53.
    Wiseman, D. M., Polverini, P. J., Kamp, D. W., and Leibovich, S. J. (1988) Transforming growth factor-beta (TGF beta) is chemotactic for human monocytes and induces their expression of angiogenic activity. Biochem. Biophys. Res. Commun. 157, 793 - 800.PubMedCrossRefGoogle Scholar
  54. 54.
    Turner, M., Chantry, D., and Feldmann, M. (1990) Transforming growth factor beta induces the production of interleukin 6 by human peripheral blood mononuclear cells. Cytokine 2, 211 - 216.PubMedCrossRefGoogle Scholar
  55. 55.
    Welch, G. R., Wong, H. L., and Wahl, S. M. (1990) Selective induction of Fc gamma RIII on human monocytes by transforming growth factor-beta. J. Immunol. 144, 3444 - 3448.PubMedGoogle Scholar
  56. 56.
    Kehrl, J. H., Wakefield, L. M., Roberts, A. B., Jakowlew, S., Alvarez-Mon,M., Derynck, R., Sporn, M. B., and Fauci, A. S. (1986) Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J. Exp. Med. 163, 1037 - 1050.Google Scholar
  57. 57.
    Wahl, S. M., Hunt, D. A., Wong, H. L., Dougherty, S., McCartney-Francis,N., Wahl, L. M., Ellingsworth, L., Schmidt, J. A., Hall, G., Roberts, A. B. and et al, (1988) Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation. J. Immunol. 140, 3026 - 3032.PubMedGoogle Scholar
  58. 58.
    Takahama, Y., Letterio, J. J., Suzuki, H., Farr, A. G. and Singer, A. (1994) Early progression of thymocytes along the CD4/CD8 developmental pathway is regulated by a subset of thymic epithelial cells expressing transforming growth factor beta. J. Exp. Med. 179, 1495 - 1506.PubMedCrossRefGoogle Scholar
  59. 59.
    Dubois, C. M., Ruscetti, F. W., Palaszynski, E. W., Falk, L. A., Oppenheim, J. J., and Keller, J. R. (1990) Transforming growth factor beta is a potent inhibitor of interleukin 1 (IL-1) receptor expression: proposed mechanism of inhibition of IL-1 action. J. Exp. Med. 172, 737 - 744.PubMedCrossRefGoogle Scholar
  60. 60.
    Turner, M., Chantry, D., Katsikis, P., Berger, A., Brennan, F. M., and Feldmann, M. (1991) Induction of the interleukin 1 receptor antagonist protein by transforming growth factor-beta. Eur. J. Immunol. 21, 1635 - 1639.PubMedCrossRefGoogle Scholar
  61. 61.
    Kehrl, J. H., Roberts, A. B., Wakefield, L. M., Jakowlew, S., Sporn, M. B., and Fauci, A. S. (1986) Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J. Immunol. 137, 3855 - 3860.PubMedGoogle Scholar
  62. 62.
    Kulkarni, A. B., Ward, J. M., Yaswen, L., Mackall, C. L., Bauer, S. R., Huh, C. G., Gress, R. E., and Karlsson, S. (1995) Transforming growth factor-beta 1 null mice. An animal model for inflammatory disorders. Am. J. Pathol. 146, 264 - 275.PubMedGoogle Scholar
  63. 63.
    Akhurst, R. J., Fitzpatrick, D. R., Gatherer, D., Lehnert, S. A., and Millan, F. A. (1990) Transforming growth factor betas in mammalian embryogenesis. Prog. Growth Factor Res. 2, 153 - 168.PubMedCrossRefGoogle Scholar
  64. 64.
    Paria, B. C., Jones, K. L., Flanders, K. C., and Dey, S. K. (1992) Localization and binding of transforming growth factor-beta isoforms in mouse preimplantation embryos and in delayed and activated blastocysts. Dev. Biol. 151, 91 - 104.PubMedCrossRefGoogle Scholar
  65. 65.
    Slager, H. G., Lawson, K. A., van den Eijnden-Van Raaij, A. J., de Laat, S. W., and Mummery, C. L. (1991) Differential localization of TGF-beta 2 in mouse preimplantation and early postimplantation development. Dev. Biol. 145, 205 - 218.Google Scholar
  66. 66.
    Rappolee, D. A., Brenner, C. A., Schultz, R., Mark, D., and Werb, Z. (1988) Developmental expression of PDGF, TGF-alpha, and TGF-beta genes in preimplantation mouse embryos. Science 241, 1823-1825.Google Scholar
  67. 67.
    Akhurst, R. J., Lehnert, S. A., Gatherer, D., and Duffie, E. (1990) The role of TGF beta in mouse development. Ann. N. Y. Acad. Sci. 593, 259 - 271.PubMedCrossRefGoogle Scholar
  68. 68.
    Heine, U., Munoz, E. F., Flanders, K. C., Ellingsworth, L. R., Lam, H. Y., Thompson, N. L., Roberts, A. B., and Sporn, M. B. (1987) Role of transforming growth factor-beta in the development of the mouse embryo. J. Cell Biol. 105 (2), 2861 - 2876.PubMedCrossRefGoogle Scholar
  69. 69.
    Millan, F. A., Denhez, F., Kondaiah, P., and Akhurst, R. J. (1991) Embryonic gene expression patterns of TGF’ beta 1, beta 2 and beta 3 suggest different developmental functions in vivo. Development 111, 131 - 143.PubMedGoogle Scholar
  70. 70.
    Flanders, K. C., Ludecke, G., Engels, S., Cissel, D. S., Roberts, A. B., Kondaiah, P., Lafyatis, R., Sporn, M. B., and Unsicker, K. (1991) Localization and actions of transforming growth factor-betas in the embryonic nervous system. Development 113, 183 - 191.PubMedGoogle Scholar
  71. 71.
    Lehnert, S. A. and Akhurst, R. J. (1988) Embryonic expression pattern of TGF beta type-1 RNA suggests both paracrine and autocrine mechanisms of action. Development 104, 263 - 273.PubMedGoogle Scholar
  72. 72.
    Fitzpatrick, D. R., Denhez, F., Kondaiah, P., and Akhurst, R. J. (1990) Differential expression of TGF beta isoforms in murine palatogenesis. Development 109, 585 - 595.PubMedGoogle Scholar
  73. 73.
    Gehris, A. L., D’ Angelo, M., and Greene, R. M. (1991) Immunodetection of the transforming growth factors beta 1 and beta 2 in the developing murine palate. Int. J. Dev. Biol. 35, 17 - 24.PubMedGoogle Scholar
  74. 74.
    Williams, J. M., Robinson, R. A., and Solursh, M. (1991) Immunohistochemical localization of TGF-B1 during morphogenetic movements of the developing mouse palate. J. Craniofacial Genetics Dev. Biol. 11, 138-145.Google Scholar
  75. 75.
    Pelton, R. W., Hogan, B. L., Miller, D. A., and Moses, H. L. (1990) Differential expression of genes encoding TGFs beta 1, beta 2, and beta 3 during murine palate formation. Dev. Biol. 141, 456-460.Google Scholar
  76. 76.
    Potts, J. D., Dagle, J. M., Walder, J. A., Weeks, D. L., and Runyan, R. B. (1991) Epithelial—mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor beta 3. Proc. Nat. Acad. Sci. USA 88, 1516 - 1520.PubMedCrossRefGoogle Scholar
  77. 77.
    Potts, J. D. and Runyan, R. B. (1989) Epithelial-mesenchymal cell transformation in the embryonic heart can be mediated, in part, by transforming growth factor beta. Dev. Biol. 134, 392 - 401.PubMedCrossRefGoogle Scholar
  78. 78.
    Timme, T. L., Truong, L. D., Merz, V. W., Krebs, T., Kadmon, D., Flanders, K. C., Park, S. H., and Thompson, T. C. (1994) Mesenchymal—epithelial interactions and transforming growth factor-beta expression during mouse prostate morphogenesis. Endocrinology 134, 1039 - 1045.PubMedCrossRefGoogle Scholar
  79. 79.
    Pelton, R. W., Saxena, B., Jones, M., Moses, H. L., and Gold, L. I. (1991) Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. J. Cell Biol. 115, 1091 - 1105.PubMedCrossRefGoogle Scholar
  80. 80.
    Akhurst, R. J., Lehnert, S. A., Faissner, A., and Duffie, E. (1990) TGF beta in murine morphogenetic processes: the early embryo and cardiogenesis. Development 108, 645 - 656.PubMedGoogle Scholar
  81. 81.
    Heimark, R. L., Twardzik, D. R., and Schwartz, S. M. (1986) Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets. Science 233, 1078 - 1080.PubMedCrossRefGoogle Scholar
  82. 82.
    Muller, G., Behrens, J., Nussbaumer, U., Bohlen, P., and Birchmeier, W. (1987) Inhibitory action of transforming growth factor beta on endothelial cells. Proc. Nat. Acad. Sci. USA 84, 5600 - 5604.PubMedCrossRefGoogle Scholar
  83. 83.
    Ohta, M., Greenberger, J. S, Anklesaria, P., Bassols, A., and Massague, J. (1987) Two forms of transforming growth factor-beta distinguished by multipotential haematopoietic progenitor cells. Nature 329, 539 - 541.PubMedCrossRefGoogle Scholar
  84. 84.
    Ottmann, O. G. and Pelus, L. M. (1988) Differential proliferative effects of transforming growth factor-beta on human hematopoietic progenitor cells. J. Immunol. 140, 2661 - 2665.PubMedGoogle Scholar
  85. 85.
    Sing, G. K., Keller, J. R., Ellingsworth, L. R., and Ruscetti, F. W. (1988) Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro. Blood 72, 1504 - 1511.PubMedGoogle Scholar
  86. 86.
    Carlino, J. A., Higley, H. R., Avis, P. D., Chu, S. S., Ogawa, Y., and Ellingsworth, L. R. (1990) Hematologic and hematopoietic changes induced by systemic administration of TGF(31, in Transforming Growth Factor-/3s: Chemistry, Biology, and Therapeutics ( Piez, K. A. and Sporn, M. B., eds.), New York Academy of Sciences, New York, pp. 330 - 333.Google Scholar
  87. 87.
    Jansen, R., Damia, G., Usui, N., Keller, J., Futami, H., Goey, H., Back, T. T., Longo, D. L., Ruscetti, F. W., and Wiltrout, R. H. (1991) Effects of recombinant transforming growth factor-beta 1 on hematologic recovery after treatment of mice with 5-fluorouracil. J. Immunol. 147, 3342 - 3347.PubMedGoogle Scholar
  88. 88.
    Carlino, J. A., Higley, H. R., Creson, J. R., Avis, P. D., Ogawa, Y., and Ellingsworth, L. R. (1992) Transforming growth factor beta 1 systemically modulates granuloid, erythroid, lymphoid, and thrombocytic cells in mice. Exp. Hematol. 20, 943 - 950.PubMedGoogle Scholar
  89. 89.
    Miller, K. L., Carlino, J. A., Ogawa, Y., Avis, P. D., and Carroll, K. G. (1992) Alterations in erythropoiesis in TGF-beta 1-treated mice. Exp. Hematol. 20, 951 - 956.PubMedGoogle Scholar
  90. 90.
    Letterio, J. J., Geiser, A. G., Kulkarni, A. B., Roche, N. S., Sporn, M. B., and Roberts, A. B. (1994) Maternal rescue of transforming growth factor-beta 1 null mice. Science 264, 1936 - 1938.PubMedCrossRefGoogle Scholar
  91. 91.
    Jennings, E. R. and Clauss, B. (1978) Maternal-fetal hemorrhage: its incidence and sensitizing effects. Am. J. Obstet. Gynecol. 131, 725 - 727.PubMedGoogle Scholar
  92. 92.
    Benahmed, M., Morera, A. M., Ghiglieri, C., Tabone, E., Menezo, Y., Hendrick, J. C., and Franchimont, P. (1993) Transforming growth factorbeta(s) in the ovary. Ann. N. Y. Acad. Sci. 687, 13 - 19.PubMedCrossRefGoogle Scholar
  93. 93.
    Chegini, N. and Flanders, K. C. (1992) Presence of transforming growth factor-beta and their selective cellular localization in human ovarian tissue of various reproductive stages. Endocrinology 130, 1707 - 1715.PubMedCrossRefGoogle Scholar
  94. 94.
    Roy, S. K., Ogren, C., Roy, C., and Lu, B. (1992) Cell-type-specific localization of transforming growth factor-beta 2 and transforming growth factor-beta 1 in the hamster ovary: differential regulation by follicle-stimulating hormone and luteinizing hormone. Biol. Reprod. 46, 595 - 606.PubMedCrossRefGoogle Scholar
  95. 95.
    Teerds, K. J. and Dorrington, J. H. (1992) Immunohistochemical localization of transforming growth factor-beta 1 and -beta 2 during follicular development in the adult rat ovary. Mol. and Cell. Endocrinology 84, R7 — R13.Google Scholar
  96. 96.
    Dorrington, J., Chuma, A. V., and Bendell, J. J. (1988) Transforming growth factor beta and follicle-stimulating hormone promote rat granulosa cell proliferation. Endocrinology 123, 353 - 359.PubMedCrossRefGoogle Scholar
  97. 97.
    May, J. V., Frost, J. P., and Schomberg, D. W. (1988) Differential effects of epidermal growth factor, somatomedin-C/insulin-like growth factor I, and transforming growth factor-beta on porcine granulosa cell deoxyribonucleic acid synthesis and cell proliferation. Endocrinology 123, 168 - 179.PubMedCrossRefGoogle Scholar
  98. 98.
    Skinner, M. K., Keski-Oja, J., Osteen, K. G., and Moses, H. L. (1987) Ovarian thecal cells produce transforming growth factor-beta which can regulate granulosa cell growth. Endocrinology 121, 786 - 792.PubMedCrossRefGoogle Scholar
  99. 99.
    Ying, S. Y., Becker, A., Ling, N., Ueno, N., and Guillemin, R. (1986) Inhibin and beta type transforming growth factor (TGF beta) have opposite modulating effects on the follicle stimulating hormone (FSH)-induced aromatase activity of cultured rat granulosa cells. Biochem. Biophys. Res. Commun. 136, 969 - 975.PubMedCrossRefGoogle Scholar
  100. 100.
    Dodson, W. C. and Schomberg, D. W. (1987) The effect of transforming growth factor-beta on follicle-stimulating hormone-induced differentiation of cultured rat granulosa cells. Endocrinology 120, 512 - 516.PubMedCrossRefGoogle Scholar
  101. 101.
    Hutchinson, L. A., Findlay, J. K., de Vos, F. L., and Robertson, D. M. (1987) Effects of bovine inhibin, transforming growth factor-beta and bovine Activin-A on granulosa cell differentiation. Biochem. Biophys. Res. Commun. 146, 1405 - 1412.PubMedCrossRefGoogle Scholar
  102. 102.
    Knecht, M., Feng, P., and Catt, K. (1987) Bifunctional role of transforming growth factor-beta during granulosa cell development. Endocrinology 120, 1243 - 1249.PubMedCrossRefGoogle Scholar
  103. 103.
    Adashi, E. Y., Resnick, C. E., Hernandez, E. R., May, J. V., Purchio, A. F., and Twardzik, D. R. (1989) Ovarian transforming growth factor-beta (TGF beta): cellular site(s), and mechanism(s) of action. Mol. Cell. Endocrinology 61, 247 - 256.CrossRefGoogle Scholar
  104. 104.
    Magoffin, D. A., Gancedo, B., and Erickson, G. F. (1989) Transforming growth factor-beta promotes differentiation of ovarian thecal-interstitial cells but inhibits androgen production. Endocrinology 125, 1951 - 1958.PubMedCrossRefGoogle Scholar
  105. 105.
    Hernandez, E. R., Hurwitz, A., Payne, D. W., Dharmarajan, A. M., Purchio, A. F., and Adashi, E. Y. (1990) Transforming growth factor-beta 1 inhibits ovarian androgen production: gene expression, cellular localization, mechanisms(s), and site(s) of action. Endocrinology 127, 2804 - 2811.PubMedCrossRefGoogle Scholar
  106. 106.
    Caubo, B., DeVinna, R. S., and Tonetta, S. A. (1989) Regulation of steroidogenesis in cultured porcine theca cells by growth factors. Endocrinology 125, 321 - 326.PubMedCrossRefGoogle Scholar
  107. 107.
    Feng, P., Catt, K. J., and Knecht, M. (1986) Transforming growth factor beta regulates the inhibitory actions of epidermal growth factor during granulosa cell differentiation. J. Biol. Chem. 261, 14,167-14, 170.Google Scholar
  108. 108.
    Knecht, M., Feng, P., and Catt, K. J. (1986) Transforming growth factor-beta regulates the expression of luteinizing hormone receptors in ovarian granulosa cells. Biochem. Biophys. Res. Commun. 139, 800 - 807.PubMedCrossRefGoogle Scholar
  109. 109.
    Mondschein, J. S., Canning, S. F., and Hammond, J. M. (1988) Effects of transforming growth factor-beta on the production of immunoreactive insulin-like growth factor I and progesterone and on [3H]thymidine incorporation in porcine granulosa cell cultures. Endocrinology 123, 1970 - 1976.PubMedCrossRefGoogle Scholar
  110. 110.
    Matsuyama, S., Shiota, K., and Takahashi, M. (1990) Possible role of transforming growth factor-beta as a mediator of luteotropic action of prolactin in rat luteal cell cultures. Endocrinology 127, 1561 - 1567.PubMedCrossRefGoogle Scholar
  111. 111.
    Tsafriri, A., Vale, W., and Hsueh, A. J. (1989) Effects of transforming growth factors and inhibin-related proteins on rat preovulatory graafian follicles in vitro. Endocrinology 125, 1857 - 1862.PubMedCrossRefGoogle Scholar
  112. 112.
    Feng, P., Catt, K. J., and Knecht, M. (1988) Transforming growth factor-beta stimulates meiotic maturation of the rat oocyte. Endocrinology 122, 181 - 186.PubMedCrossRefGoogle Scholar
  113. 113.
    Howe, P. H., Draetta, G., and Leof, E. B. (1991) Transforming growth factor beta 1 inhibition of p34cdc2 phosphorylation and histone H1 kinase activity is associated with Gl/S-phase growth arrest. Mol. Cell. Biol. 11, 1185 - 1194.PubMedGoogle Scholar
  114. 114.
    Gabrielli, B. G., Roy, L. M., and Mailer, J. L. (1993) Requirement for Cdk2 in cytostatic factor-mediated metaphase II arrest. Science 259, 1766 - 1769.PubMedCrossRefGoogle Scholar
  115. 115.
    Hampl, A. and Eppig, J. J. (1995) Analysis of the mechanism(s) of metaphase I arrest in maturing mouse oocytes. Development 121, 925— 933.Google Scholar
  116. 116.
    Altman, D. J., Schneider, S. L., Thompson, D. A., Cheng, H. L., and Tomasi, T. B. (1990) A transforming growth factor beta 2 (TGF-beta 2)-like immunosuppressive factor in amniotic fluid and localization of TGF-beta 2 mRNA in the pregnant uterus. J. Exp. Med. 172, 1391 - 1401.PubMedCrossRefGoogle Scholar
  117. 117.
    Tamada, H., McMaster, M. T., Flanders, K. C., Andrews, G. K., and Dey, S. K. (1990) Cell type-specific expression of transforming growth factor-beta 1 in the mouse uterus during the periimplantation period. Mol. Endocrinology 4, 965 - 972.CrossRefGoogle Scholar
  118. 118.
    Dungy, L. J., Siddiqi, T. A., and Khan, S. (1991) Transforming growth factor-beta 1 expression during placental development. Am. J. Obstet. Gynecol. 165 (1), 853 - 857.PubMedGoogle Scholar
  119. 119.
    Das, S. K., Flanders, K. C., Andrews, G. K., and Dey, S. K. (1992) Expression of transforming growth factor-beta isoforms (beta 2 and beta 3) in the mouse uterus: analysis of the periimplantation period and effects of ovarian steroids. Endocrinology 130, 3459 - 3466.PubMedCrossRefGoogle Scholar
  120. 120.
    Lea, R. G., Flanders, K. C., Harley, C. B., Manuel, J., Banwatt, D., and Clark, D. A. (1992) Release of a transforming growth factor (TGF)-beta 2-related suppressor factor from postimplantation murine decidual tissue can be correlated with the detection of a subpopulation of cells containing RNA for TGF-beta 2. J. Immunol. 148, 778 - 787.PubMedGoogle Scholar
  121. 121.
    Manova, K., Paynton, B. V., and Bachvarova, R. F. (1992) Expression of activins and TGF beta 1 and beta 2 RNAs in early postimplantation mouse embryos and uterine decidua. Mech. Dey. 36, 141 - 152.CrossRefGoogle Scholar
  122. 122.
    Graham, C. H. and Lala, P. K. (1991) Mechanism of control of trophoblast invasion in situ. J. Cell. Physiol. 148, 228 - 234.PubMedCrossRefGoogle Scholar
  123. 123.
    Clark, D. A., Falbo, M., Rowley, R. B., Banwatt, D., and Stedronska-Clark, J. (1988) Active suppression of host-vs graft reaction in pregnant mice. IX. Soluble suppressor activity obtained from allopregnant mouse decidua that blocks the cytolytic effector response to IL-2 is related to transforming growth factor-beta. J. Immunol. 141, 3833 - 3840.PubMedGoogle Scholar
  124. 124.
    Clark, D. A., Flanders, K. C., Banwatt, D., Millar-Book, W., Manuel, J., Stedronska-Clark, J., and Rowley, B. (1990) Murine pregnancy decidua produces a unique immunosuppressive molecule related to transforming growth factor beta-2. J. Immunol. 144, 3008.-3014.Google Scholar
  125. 125.
    Skinner, M. K. (1991) Cell-cell interactions in the testis. Endocrine Rev. 12, 45 - 77.CrossRefGoogle Scholar
  126. 126.
    Skinner, M. K., Norton, J. N., Mullaney, B. P., Rosselli, M., Whaley, P. D., and Anthony, C. T. (1991) Cell-cell interactions and the regulation of testis function. Ann. N. Y. Acad. Sci. 637, 354 - 363.PubMedCrossRefGoogle Scholar
  127. 127.
    Gautier, C., Levacher, C., Avallet, O., Vigier, M., Rouiller-Fabre, V., Lecerf, L., Saez, J., and Habert, R. (1994) Immunohistochemical localization of transforming growth factor-beta 1 in the fetal and neonatal rat testis. Mol. Cell. Endocrinology 99, 55 - 61.CrossRefGoogle Scholar
  128. 128.
    Mullaney, B. P. and Skinner, M. K. (1993) Transforming growth factor-beta (beta 1, beta 2, and beta 3) gene expression and action during pubertal development of the seminiferous tubule: potential role at the onset of spermatogenesis. Mol. Endocrinol. 7, 67 - 76.PubMedCrossRefGoogle Scholar
  129. 129.
    Watrin, F., Scotto, L., Assoian, R. K., and Wolgemuth, D. J. (1991) Cell lineage specificity of expression of the murine transforming growth factor beta 3 and transforming growth factor beta 1 genes. Cell Growth Differ. 2, 77 - 83.PubMedGoogle Scholar
  130. 130.
    Avallet, O., Vigier, M., Perrard-Sapori, M. H., and Saez, J. M. (1987) Transforming growth factor beta inhibits Leydig cell functions. Biochem. Biophys. Res. Commun. 146, 575 - 581.PubMedCrossRefGoogle Scholar
  131. 131.
    Fauser, B. C. and Hsueh, A. J. (1988) Effect of transforming growth factor-beta on human chorionic gonadotropin induced testosterone production by cultured rat testicular cells. Life Sci. 43, 1363 - 1370.PubMedCrossRefGoogle Scholar
  132. 132.
    Lin, T., Blaisdell, J., and Haskell, J. F. (1987) Transforming growth factor-beta inhibits Leydig cell steroidogenesis in primary culture. Biochem. Biophys. Res. Commun. 146, 387 - 394.PubMedCrossRefGoogle Scholar
  133. 133.
    Morera, A. M., Cochet, C., Keramidas, M., Chauvin, M. A., de Peretti, E., and Benahmed, M. (1988) Direct regulating effects of transforming growth factor beta on the Leydig cell steroidogenesis in primary culture. J. Steroid Biochem. 30, 443 - 447.PubMedCrossRefGoogle Scholar
  134. 134.
    Skinner, M. K. and Moses, H. L. (1989) Transforming growth factor beta gene expression and action in the seminiferous tubule: peritubular cellSertoli cell interactions. Mol. Endocrinol. 3, 625 - 634.PubMedCrossRefGoogle Scholar
  135. 135.
    Teerds, K. J. and Dorrington, J. H. (1993) Localization of transforming growth factor beta 1 and beta 2 during testicular development in the rat. Biol. Reprod. 48, 40 - 45.PubMedCrossRefGoogle Scholar
  136. 136.
    Matzuk, M. M., Finegold, M. J., Mather, J. P., Krummen, L., Lu, H., and Bradley, A. (1994) Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice. Proc. Nat. Acad. Sci. USA 91, 8817 - 8821.PubMedCrossRefGoogle Scholar
  137. 137.
    Plata-Salaman, C. R., Oomura, Y., and Kai, Y. (1988) Tumor necrosis factor and interleukin-1 beta: suppression of food intake by direct action in the central nervous system. Brain Res. 448, 106 - 114.PubMedCrossRefGoogle Scholar
  138. 138.
    Tracey, K. J., Morgello, S., Koplin, B., Fahey, T. J., 3d, Fox, J., Aledo, A., Manogue, K. R., and Cerami, A. (1990) Metabolic effects of cachectin/ tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. J. Clin. Invest. 86, 2014 - 2024.Google Scholar
  139. 139.
    Nicholson, A. C. and Hajjar, D. P. (1992) Transforming growth factor-beta up-regulates low density lipoprotein receptor-mediated cholesterol metabolism in vascular smooth muscle cells. J. Biol. Chem. 267, 25982 - 25987.PubMedGoogle Scholar
  140. 140.
    Dajani, A. S., Taubert, K. A., Gerber, M. A., Shulman, S. T., Ferrien, P., Freed, M., Takahashi, M., Bierman, F. Z., Karchmer, A. W., Wilson, W., et al. (1993) Diagnosis and therapy of Kawasaki disease in children. Circulation 87, 1776 - 1780.PubMedCrossRefGoogle Scholar
  141. 141.
    Furukawa, S., Imai, K., Matsubara, T., Yone, K., Yachi, A., Okumura, K., and Yabuta, K. (1992) Increased levels of circulating intercellular adhesion molecule 1 in Kawasaki disease. Arthritis Rheum. 35, 672 - 677.PubMedCrossRefGoogle Scholar
  142. 142.
    Furukawa, S., Matsubara, T., Yone, K., Hirano, Y., Okumura, K., and Yabuta, K. (1992) Kawasaki disease differs from anaphylactoid purpura and measles with regard to tumour necrosis factor-alpha and interleukin 6 in serum. Eur. J. Pediatr. 151, 44 - 47.PubMedCrossRefGoogle Scholar
  143. 143.
    Gulick, T., Chung, M. K., Pieper, S. J., Lange, L. G., and Schreiner, G. F. (1989) Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte beta-adrenergic responsiveness. Proc. Nat. Acad. Sci. USA 86, 6753 - 6757.PubMedCrossRefGoogle Scholar
  144. 144.
    Lefer, A. M., Tsao, P., Aoki, N., and Palladino, M. A., Jr. (1990) Mediation of cardioprotection by transforming growth factor-beta. Science 249, 61 - 64.PubMedCrossRefGoogle Scholar
  145. 145.
    Roberts, A. B., Roche, N. S., Winokur, T. S., Burmester, J. K., and Sporn, M. B. (1992) Role of transforming growth factor-beta in maintenance of function of cultured neonatal cardiac myocytes. Autocrine action and reversal of damaging effects of interleukin-1. J. Clin. Invest. 90, 2056 - 2062.PubMedCrossRefGoogle Scholar
  146. 146.
    Lefer, A. M., Ma, X. L., Weyrich, A. S., and Scalia, R. (1993) Mechanism of the cardioprotective effect of transforming growth factor beta 1 in feline myocardial ischemia and reperfusion. Proc. Nat. Acad. Sci. USA 90, 1018 - 1022.PubMedCrossRefGoogle Scholar
  147. 147.
    Ridley, A. J., Davis, J. B., Stroobant, P., and Land, H. (1989) Transforming growth factors-beta 1 and beta 2 are mitogens for rat Schwann cells. J. Cell Biol. 109 (2), 3419 - 24.PubMedCrossRefGoogle Scholar
  148. 148.
    Eccleston, P. A., Jessen, K. R., and Mirsky, R. (1989) Transforming growth factor-beta and gamma-interferon have dual effects on growth of peripheral glia. J. Neurosci. Res. 24, 524 - 530.Google Scholar
  149. 149.
    Rogister, B., Delree, P., Leprince, P., Martin, D., Sadzot, C., Malgrange, B., Munaut, C., Rigo, J. M., Lefebvre, P. P., Octave, J. N. and et al, (1993) Transforming growth factor beta as a neuronoglial signal during peripheral nervous system response to injury. J. Neurosci. Res. 34, 32 - 43.PubMedCrossRefGoogle Scholar
  150. 150.
    Schubert, D. (1992) Synergistic interactions between transforming growth factor beta and fibroblast growth factor regulate Schwann cell mitosis. J. Neurobiol. 23, 143 - 148.PubMedCrossRefGoogle Scholar
  151. 151.
    Threadgill, D. W., Dlugosz, A. A., Hansen, L. A., Tennenbaum, T., Lichti, U., Yee, D., LaMantia, C., Mourton, T., Herrup, K., Harris, R. C., Barnard, J. A., Yuspa, S., Coffey, R. J., and Magnuson, T. (1995) Targeted disruption of mouse EGF Receptor: Effect of genetic background on mutant phenotype. Science 269, 230 - 234.PubMedCrossRefGoogle Scholar
  152. 152.
    Sibilia, M. and Wagner, E. F. (1995) Strain-dependent epithelial defects in mice lacking the EGF receptor. Science 269, 234 - 238.PubMedCrossRefGoogle Scholar
  153. 153.
    Winnier, G., Blessing, M., Labosky, P. A., and Hogan, B. L. M. (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Devel. 9, 2105 - 2116.PubMedCrossRefGoogle Scholar
  154. 154.
    Derynck, R., Lindquist, P. B., Lee, A., Wen, D., Tamm, J., Graycar, J. L., Rhee, L., Mason, A. J., Miller, D. A., Coffey, R. J., et al, (1988) A new type of transforming growth factor-beta, TGF-beta 3. EMBO J. 7, 3737 - 3743.Google Scholar
  155. 155.
    ten Dijke, P., Hansen, P., Iwata, K. K., Pieler, C., and Foulkes, J. G. (1988) Identification of another member of the transforming growth factor type beta gene family. Proc. Nat. Acad. Sci. USA 85, 4715 - 4719.PubMedCrossRefGoogle Scholar
  156. 156.
    Pelton, R. W., Dickinson, M. E., Moses, H. L., and Hogan, B. L. (1990) In situ hybridization analysis of TGF beta 3 RNA expression during mouse development: comparative studies with TGF beta 1 and beta 2. Development 110, 609 - 620.PubMedGoogle Scholar
  157. 157.
    Flanders, K. C., Ludecke, G., Engels, S., Cissel, D. S., Roberts, A. B., Kondaiah, P., Lafyatis, R., Sporn, M. B., and Unsicker, K. (1991) Localization and actions of transforming growth factor-beta s in the embryonic nervous system. Development 113, 183 - 191.Google Scholar
  158. 158.
    Vassalli, A., Matzuk, M. M., Gardner, H. A., Lee, K. F., and Jaenisch, R. (1994) Activin/inhibin beta B subunit gene disruption leads to defects in eyelid development and female reproduction. Genes Devel. 8, 414 - 427.PubMedCrossRefGoogle Scholar
  159. 159.
    Matzuk, M. M., Kumar, T. R., Vassalli, A., Bickenbach, J. R., Roop, D. R., Jaenisch, R., and Bradley, A. (1995) Functional analysis of activins during mammalian development. Nature 374, 354 - 356.PubMedCrossRefGoogle Scholar
  160. 160.
    Matzuk, M. M., Finegold, M. J., Su, J. G., Hsueh, A. J., and Bradley, A. (1992) Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 360, 313 - 319.PubMedCrossRefGoogle Scholar
  161. 161.
    Kingsley, D. M., Bland, A. E., Grubber, J. M., Marker, P. C., Russell, L. B., Copeland, N. G., and Jenkins, N. A. (1992) The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF beta superfamily. Cell 71, 399 - 410.PubMedCrossRefGoogle Scholar
  162. 162.
    Dudley, A. T., Lyons, K. M., and Robertson, E. J. (1995) A requirement for bone morphogenetic protein-7 during development of mammalian kidney and eye. Genes Devel. 9, 2795 - 2807.PubMedCrossRefGoogle Scholar
  163. 163.
    Luo, G., Hofmann, C., Bronckers, A. L. J. J., Sohocki, M., Bradley, A., and Karsenty, G. (1995) BMP-7 is an inducer of nephrogenesis and is also required for eye development and skeletal patterning. Genes Devel. 9, 2808 - 2820.PubMedCrossRefGoogle Scholar
  164. 164.
    Ames, B. N., Gold, L. S., and Willett, W. C. (1995) The causes and prevention of cancer. Proc. Nat. Acad. Sci. USA 92, 5258 - 5265.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Suhas Kallapur
  • Marcia Shull
  • Thomas Doetschman

There are no affiliations available

Personalised recommendations