Skip to main content

Transgenic Mouse Models for Hematopoietic Tumorigenesis

  • Conference paper

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 141))

Abstract

The development of transgenic mice carrying specific cancer-promoting genes represents a major advance in molecular oncology (for reviews, see Cory and Adams, 1988; Hanahan, 1987). In principle, the effect of a particular oncogene can be assessed for every cell type within the animal by this approach. The transgene can either be linked to a catholic regulatory sequence and expressed throughout all tissues, or its expression can be confined to a particular cell lineage by fusing it to a tissue-specific promoter/enhancer control element. Our own interests center on hematopoietic neoplasia, so we have produced transgenic mice harboring oncogenes targeted for constitutive expression in hematopoietic cells. The principal regulatory sequence we have used is the immunoglobulin (Ig) heavy chain enhancer (Eµ). While the function of this sequence is to direct expression of Ig heavy chain (IgH) genes in B lymphoid cells, it may also be active in at least some T lymphoid and even myeloid cells since the IgH locus is transcriptionally active in certain T and myeloid cell lines (Kemp et al, 1980a) and thymocytes (Kemp et al, 1980b) and an immunoglobulin µ transgene can be expressed in T as well as B cells (Grosschedl et al, 1984).

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S, Palmiter RD and Brinster RL (1985) The c-myc gene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318: 533–538

    Article  PubMed  CAS  Google Scholar 

  • Alexander W, Schrader JW and Adams JM (1987) Expression of the c-myc oncogene under control of an immunoglobulin enhancer in Eµ-myc transgenic mice. Mol Cell Biol 7: 1436–1444

    PubMed  CAS  Google Scholar 

  • Ben-Neriah Y and Baltimore D (1986) Structural modification of c-abl in lymphoma and leukemia. Curr Topics Microbiol Immunol 132: 81–89

    Article  CAS  Google Scholar 

  • Bos JL, Toksoz D, Marshall CJ, Verlaande Vries M, Veeneman GH, van der Eb AJ, van Boom JH, Janssen JWG and Steenvorden ACM (1985) Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. Nature 315: 726–730

    Article  PubMed  CAS  Google Scholar 

  • Cook WD (1982) Rapid thymomas induced by Abelson murine leukemia virus. Proc Natl Acad Sci USA 79: 2917–2921

    Article  PubMed  CAS  Google Scholar 

  • Corcoran LM, Cory S and Adams JM (1985) Transposition of the immunoglobulin heavy chain enhancer to the myc oncogene in a murine plasmacytoma. Cell 40: 71–79

    Article  PubMed  CAS  Google Scholar 

  • Cory S (1986) Activation of cellular oncogenes in hemopoietic cells by chromosome translocations. Adv Cancer Res 47: 189–234

    Article  PubMed  CAS  Google Scholar 

  • Cory S and Adams JM (1988) Transgenic mice and oncogenesis. Ann Rev Immunol in press

    Google Scholar 

  • Dyall-Smith D and Cory S (1987). Transformation of bone marrow cells from Eµ-myc transgenic mice by Abelson murine leukemia virus and Harvey murine sarcoma virus. Oncogene Res in press

    Google Scholar 

  • Farr CJ, Saiki RK, Erlich HA, McCormick F and Marshall CJ (1988) Analysis of RAS gene mutations in acute myeloid leukemia by polymerase chain reaction and oligonucleotide probes. Proc Natl Acad Sci USA 85: 1629–1633

    Article  PubMed  CAS  Google Scholar 

  • Grosschedl R, Weaver D, Baltimore D and Costantini F (1984) Introduction of a µ immunoglobulin gene into the mouse germ line: Specific expression in lymphoid cells and synthesis of functional antibody. Cell 38: 647–658

    Article  PubMed  CAS  Google Scholar 

  • Guerrero I, Villasante A, D’Eustachio P and Pellicer A (1984) Isolation, preliminary characterisation, and chromosomal localization of the activated mouse N-ras gene from a carcinogen-induced thymic lymphoma. Science 225: 1041–1043

    Article  PubMed  CAS  Google Scholar 

  • Hanahan D (1986) Oncogenesis in transgenic mice. In: Kahn P and Graf T (eds) Oncogenes and Growth Control. Springer, Berlin, pp 349–363

    Chapter  Google Scholar 

  • Hariharan IK and Adams JM (1987) cDNA sequence for human bcr, the gene that translocates to the abl oncogene in chronic myeloid leukaemia. EMBO J 6: 115–119

    PubMed  CAS  Google Scholar 

  • Harris AW, Pinkert CA, Crawford MC, Langdon WY, Brinster RL and Adams JM (1988) The Eµ-myc transgenic mouse. A model for high incidence spontaneous lymphoma and leukemia of early B cells. J Exp Med in press

    Google Scholar 

  • Kemp D, Harris AW, Cory S and Adams JM (1980a) Expression of the immunoglobulin Cµ gene in mouse T and B lymphoid and myeloid cell lines. Proc Natl Acad Sci USA 77: 2876–2880

    Article  PubMed  CAS  Google Scholar 

  • Kemp DJ, Wilson A, Harris AW and Shortman K (1980b) The immunoglobulin µ constant region gene is expressed in mouse thymocytes. Nature 286: 168–170

    Article  PubMed  CAS  Google Scholar 

  • Konopka JB, Watanabe SM and Witte ON (1984) An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell 37: 1035–1042

    Article  PubMed  CAS  Google Scholar 

  • Langdon WY, Harris AW, Cory S and Adams JM (1986) The c-myc oncogene perturbs B lymphocyte development in Eµ-myc transgenic mice. Cell 47: 11–18.

    Article  PubMed  CAS  Google Scholar 

  • Nordan RP and Potter M (1986) A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro. Science 233: 566–569

    Article  PubMed  CAS  Google Scholar 

  • O’Garra A, Umland S, DeFrance T and Christiansen J (1988) ‘B-cell factors’ are pleiotropic. Immunol Today 9: 45–54

    Google Scholar 

  • Potter M, Sklar MD and Rowe WP (1973) Rapid viral induction of plasmacytomas in pristane-primed BALB/c mice. Science 182: 592–594

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg N (1982) Abelson leukemia virus. Curr Topics Microbiol Immunol 101: 95–126

    Article  CAS  Google Scholar 

  • Schwab M (1986) Amplification of proto-oncogenes and tumor progression. In: Kahn P and Graf T (eds) Oncogenes and Growth Control. Springer, Berlin, pp332–339

    Chapter  Google Scholar 

  • Schwab M, Varmus HE and Bishop JM (1985) Human N-myc gene contributes to neoplastic transformation of mammalian cells in culture. Nature 316: 160–162

    Article  PubMed  CAS  Google Scholar 

  • Shtivelman E, Lifshitz B, Gale RP and Canaani E (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 315: 550–554

    Article  PubMed  CAS  Google Scholar 

  • Small MB, Hay N, Schwab M and Bishop JM (1987) Neoplastic transformation by the human gene N-myc. Mol Cell Biol 7: 1638–1645

    PubMed  CAS  Google Scholar 

  • Vaux DL, Adams JM, Alexander WS and Pike BL (1987) Immunologic competence of B cells subjected to constitutive c-myc oncogene expression in immunoglobulin heavy chain enhancer myc transgenic mice. J Immunol 139: 3854–3860

    PubMed  CAS  Google Scholar 

  • Yancopoulos GD, Nisen PD, Tesfaye A, Kohl NE, Goldfarb MP and Alt FW (1985) N-myc can cooperate with ras to transform normal cells in culture. Proc Nat Acad Sci USA 82: 5455–5459

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman KA, Yancopoulos GD, Collum RG, Smith RK, Kohl NE, Davis KA, Nau MM, Witte ON, Toran-Allerand D, Gee CE, Minna JD and Alt FW (1986) Differential expression of myc family genes during murine development. Nature 319: 780–783

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Berlin · Heidelberg

About this paper

Cite this paper

Harris, A.W. et al. (1988). Transgenic Mouse Models for Hematopoietic Tumorigenesis. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1988. Current Topics in Microbiology and Immunology, vol 141. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74006-0_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-74006-0_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-74008-4

  • Online ISBN: 978-3-642-74006-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics