Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Technical Report
  • Published:

Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish

Oncogene volume 27, pages 4242–4248 (2008)Cite this article

Abstract

The zebrafish has emerged as a powerful genetic model of cancer, but has been limited by the use of stable transgenic approaches to induce disease. Here, a co-injection strategy is described that capitalizes on both the numbers of embryos that can be microinjected and the ability of transgenes to segregate together and exert synergistic effects in forming tumors. Using this mosaic transgenic approach, gene pathways involved in tumor initiation and radiation sensitivity have been identified.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Berghmans S, Murphey RD, Wienholds E, Neuberg D, Kutok JL, Fletcher CD et al. (2005). tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors. Proc Natl Acad Sci USA 102: 407–412.

    Article  CAS  Google Scholar 

  • Burns CE, Traver D, Mayhall E, Shepard JL, Zon LI . (2005). Hematopoietic stem cell fate is established by the Notch–Runx pathway. Genes Dev 19: 2331–2342.

    Article  CAS  Google Scholar 

  • Halloran MC, Sato-Maeda M, Warren JT, Su F, Lele Z, Krone PH et al. (2000). Laser-induced gene expression in specific cells of transgenic zebrafish. Development 127: 1953–1960.

    CAS  Google Scholar 

  • Haramis AP, Hurlstone A, van der Velden Y, Begthel H, van den Born M, Offerhaus GJ et al. (2006). Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia. EMBO Rep 7: 444–449.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jessen JR, Jessen TN, Voge SS, Lin S . (2001). Concurrent expression of recombination activating genes 1 and 2 in zebrafish olfactory sensory neurons. Genesis: the Journal of Genetics and Development 29: 156–162.

    Article  CAS  Google Scholar 

  • Kratz E, Eimon PM, Mukhyala K, Stern H, Zha J, Strasser A et al. (2006). Functional characterization of the Bcl-2 gene family in the zebrafish. Cell Death Differ 13: 1631–1640.

    Article  CAS  Google Scholar 

  • Langenau DM, Feng H, Berghmans S, Kanki JP, Kutok JL, Look AT . (2005a). Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia. Proc Natl Acad Sci USA 102: 6068–6073.

    Article  CAS  Google Scholar 

  • Langenau DM, Jette C, Berghmans S, Palomero T, Kanki JP, Kutok JL et al. (2005b). Suppression of apoptosis by bcl-2 overexpression in lymphoid cells of transgenic zebrafish. Blood 105: 3278–3285.

    Article  CAS  Google Scholar 

  • Langenau DM, Keefe MD, Storer NY, Guyon JR, Kutok JL, Le X et al. (2007). Effects of RAS on the genesis of embryonal rhabdomyosarcoma. Genes Dev 21: 1382–1389.

    Article  CAS  Google Scholar 

  • Langenau DM, Traver D, Ferrando AA, Kutok JL, Aster JC, Kanki JP et al. (2003). Myc-induced T cell leukemia in transgenic zebrafish. Science 299: 887–890.

    Article  CAS  Google Scholar 

  • Le X, Langenau DM, Keefe MD, Kutok JL, Neuberg DS, Zon LI . (2007). Heat shock-inducible Cre/Lox approaches to induce diverse types of tumors and hyperplasia in transgenic zebrafish. Proc Natl Acad Sci USA 104: 9410–9415.

    Article  CAS  Google Scholar 

  • Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T et al. (2000). Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288: 1053–1058.

    Article  CAS  Google Scholar 

  • Patton EE, Widlund HR, Kutok JL, Kopani KR, Amatruda JF, Murphey RD et al. (2005). BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr Biol 15: 249–254.

    Article  CAS  Google Scholar 

  • Pyati UJ, Webb AE, Kimelman D . (2005). Transgenic zebrafish reveal stage-specific roles for Bmp signaling in ventral and posterior mesoderm development. Development 132: 2333–2343.

    Article  CAS  Google Scholar 

  • Sabaawy HE, Azuma M, Embree LJ, Tsai HJ, Starost MF, Hickstein DD . (2006). TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia. Proc Natl Acad Sci USA 103: 15166–15171.

    Article  CAS  Google Scholar 

  • Traver D, Paw BH, Poss KD, Penberthy WT, Lin S, Zon LI . (2003). Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants. Nat Immunol 4: 1238–1246.

    Article  CAS  Google Scholar 

  • Traver D, Winzeler A, Stern HM, Mayhall EA, Langenau DM, Kutok JL et al. (2004). Effects of lethal irradiation in zebrafish and rescue by hematopoietic cell transplantation. Blood 104: 1298–1305.

    Article  CAS  Google Scholar 

  • Tropepe V, Coles BL, Chiasson BJ, Horsford DJ, Elia AJ, McInnes RR et al. (2000). Retinal stem cells in the adult mammalian eye. Science 287: 2032–2036.

    Article  CAS  Google Scholar 

  • Xiao T, Shoji W, Zhou W, Su F, Kuwada JY . (2003). Transmembrane sema4E guides branchiomotor axons to their targets in zebrafish. J Neurosci 23: 4190–4198.

    Article  CAS  Google Scholar 

  • Yang HW, Kutok JL, Lee NH, Piao HY, Fletcher CD, Kanki JP et al. (2004). Targeted expression of human MYCN selectively causes pancreatic neuroendocrine tumors in transgenic zebrafish. Cancer Res 64: 7256–7262.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Anna Burrows for expert technical help and David Bellovin and David Adamovich for critical review of this manuscript. DM Langenau is the Edmond J Safra Foundation Fellow from the Irvington Institute and CJ Ceol is supported by a Damon Runyon Fellowship (DRG-1855-05). Funding for this work was provided by NIH Grant 5R01 CA103846-02 (LI Zon), #1RO1 CA119066-01, CA93152-05, CA104605-03, HL-088664 and CA68484-11 (AT Look), #1KO1 DK074555-01 (CA Jette).

Author information

Author notes

  1. M D Keefe, N Y Storer and C A Jette: These authors contributed equally to work presented.

Authors and Affiliations

  1. Stem Cell Program and Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA, USA

    D M Langenau, M D Keefe, N Y Storer, A C H Smith, C J Ceol, C Bourque & L I Zon

  2. Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    C A Jette & A T Look

Authors
  1. D M Langenau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M D Keefe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Y Storer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C A Jette
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A C H Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C J Ceol
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Bourque
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A T Look
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L I Zon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D M Langenau.

Additional information

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Langenau, D., Keefe, M., Storer, N. et al. Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish. Oncogene 27, 4242–4248 (2008). https://doi.org/10.1038/onc.2008.56

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2008.56

Keywords

This article is cited by

Search

Advanced search

Quick links