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Genetic reporter system for oncogenic Igh–Myc translocations in mice

Oncogene volume 29, pages 4113–4120 (2010)Cite this article

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Abstract

The Myc-deregulating chromosomal T(12;15)(Igh–Myc) translocation, the hallmark mutation of inflammation- and interleukin 6-dependent mouse plasmacytoma (PCT), is the premier model of cancer-associated chromosomal translocations because it is the only translocation in mice that occurs spontaneously (B lymphocyte lineage) and with predictably high incidence (∼85% of PCT), and has a direct counterpart in humans: Burkitt lymphoma t(8;14)(q24;q32) translocation. Here, we report on the development of a genetic system for the detection of T(12;15)(Igh–Myc) translocations in plasma cells of a mouse strain in which an enhanced green fluorescent protein (GFP)-encoding reporter gene has been targeted to Myc. Four of the PCTs that developed in the newly generated translocation reporter mice, designated iGFP5′Myc, expressed GFP consequent to naturally occurring T(12;15) translocation. GFP expression did not interfere with tumor development or the deregulation of Myc on derivative 12 of translocation, der (12), because the reporter gene was allocated to the reciprocal product of translocation, der (15). Although the described reporter gene approach requires refinement before T(12;15) translocations can be quantitatively detected in vivo, including in B lymphocyte lineage cells that have not yet completed malignant transformation, our findings provide proof of principle that reporter gene tagging of oncogenes in gene-targeted mice can be used to elucidate unresolved questions on the occurrence, distribution and trafficking of cells that have acquired cancer-causing chromosomal translocations of great relevance for humans.

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Acknowledgements

We thank our colleagues from NCI and NIAID, NIH for their contributions to this project: Tina Willington, Vaishali Jarral and Wendy DuBois for genotyping and assistance with the mouse experiments; Eileen Southon for gene targeting; Dr Alexander L Kovalchuk for advice on PCR analysis and providing primers; Drs Sung Sup Park and Santiago Silva for contributions to early stages of this project; and Drs Michael Potter and Beverly Mock for stimulating discussion and laboratory support. For assistance with transfer, cryopreservation, maintenance and rederivation of mice under SPF conditions, we thank: Ling Hu, CCOM, Iowa City, Iowa; the staff of the Jackson Laboratory, Bar Harbor, Maine; and the Office of Animal Resources, CCOM, particularly Dr Kem Singletary and James Hynes. We also thank Lorraine Tygrett, CCOM for assistance with flow cytometry. This work was supported, in part, by the Intramural Research Program of the NIH (LT, RC, TR) and Award Number P50CA097274 from the National Cancer Institute (SJ).

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Author notes

  1. J S Kim

    Present address: 7Current address: Korea Research Institute of Bioscience and Biotechnology (KRIBB), 52 Oun, Yusong, Taejon 305-333, Republic of Korea.,

  2. M Takizawa and J S Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Genetics, Center for Cancer Research (CCR), National Cancer Institute (NCI), Bethesda, MD, USA

    M Takizawa & J S Kim

  2. Genomics & Immunity, National Institute of Arthritis and Musculoskeletal Disease, Bethesda, MD, USA

    M Takizawa & R Casellas

  3. Mouse Cancer Genetics Program, CCR, NCI, Bethesda, MD, USA

    L Tessarollo

  4. Genetics Branch, CCR, NCI, National Institutes of Health, Bethesda, MD, USA

    N McNeil & T Ried

  5. Department of Pathology, The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA

    T J Waldschmidt & S Janz

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  1. M Takizawa
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Correspondence to S Janz.

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Takizawa, M., Kim, J., Tessarollo, L. et al. Genetic reporter system for oncogenic Igh–Myc translocations in mice. Oncogene 29, 4113–4120 (2010). https://doi.org/10.1038/onc.2010.150

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