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AID and RAG1 do not contribute to lymphomagenesis in Eμ c-myc transgenic mice

Oncogene volume 27, pages 4752–4756 (2008)Cite this article

Abstract

DNA breaks caused by recombination-activating gene 1 (RAG1) and activation-induced cytidine deaminase (AID) induce c-myc/immunoglobulin (Ig) heavy chain chromosomal translocations and thereby stimulate lymphomagenesis. However, constitutive expression of c-myc alone is not sufficient to induce lymphomas. Because RAG1 and AID activity occurs outside of Ig genes, we assessed whether these enzymes provide the secondary genetic lesions in Eμ c-myc transgenic mice to promote lymphoma development. We found that the tumor incidence and tumor phenotype in Eμ c-myc transgenic mice is similar in AID+/+, AID+/− and AID−/− backgrounds in both specific pathogen-free and conventional animal facilities, indicating that AID does not contribute to lymphoma development in Eμ c-myc transgenic mice. To examine the role of RAG proteins in Eμ c-myc mice, we examined Eμ c-myc transgenic mice that harbor the Ig-HEL heavy- and light-chain transgenes, and thus have reduced RAG expression in B cells. We found that tumor incidence was not affected by these Ig transgenes. However, we found that RAG1−/− Eμ c-myc mice exhibited accelerated tumor development compared to controls. This data combined with our finding that Eμ c-myc mice lived longer in the conventional facility than in the specific pathogen-free facility suggest an immune-mediated activity that suppresses lymphoma development.

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Acknowledgements

We are grateful to Dr Matthew D Scharff and Dr Gillian Wu and to the Martin laboratory for helpful discussions and to Maribel Berru for technical help. This research is supported by a grant from the Canadian Cancer Society (16080) to AM, who is also supported by a Canada Research Chair award. AZ is supported by a Canadian Institute of Health Research Scholarship, whereas RMN is a Lymphoma Foundation Canada Fellow.

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Authors and Affiliations

  1. Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Canada

    R M Nepal, A Zaheen, W Basit, L Li, S A Berger & A Martin

  2. Arthritis and Autoimmunity Research Centre, University Health Network, Toronto, Canada

    S A Berger

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  1. R M Nepal
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  2. A Zaheen
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  3. W Basit
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  4. L Li
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Correspondence to A Martin.

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

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Nepal, R., Zaheen, A., Basit, W. et al. AID and RAG1 do not contribute to lymphomagenesis in Eμ c-myc transgenic mice. Oncogene 27, 4752–4756 (2008). https://doi.org/10.1038/onc.2008.111

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