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Loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice

Oncogene volume 23, pages 4655–4661 (2004)Cite this article

Abstract

Ataxia Telangiectasia (A-T) is an autosomal recessive disease caused by loss of function of the protein kinase ATM. Atm-deficient mice display several phenotypes consistent with the human disease, including predisposition to cancer, growth retardation, cell-proliferation defects and infertility. A-T patients have a several hundred fold increased risk of developing lymphomas and leukemias, which are typically highly invasive. By reducing homologous recombination through genetic deletion of the Rad52 protein, we were able to decrease substantially the development of T-cell lymphomas in Atm−/− mice, resulting in an increased life span of the double mutant mice. Additionally, we were able to partially rescue the T-cell development of Atm−/− mice. Other phenotypes, including growth defects, genomic instability, infertility and radiosensitivity, were not rescued. Our results suggest that excessive recombination is an important contributor to tumorigenesis in A-T.

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Acknowledgements

We thank A Pastink for providing Rad52−/− mice. Special thanks go to M. McConnell and J. Chun for SKY analysis of MEFs and helpful discussions. K.T. is supported by the Deutsche Forschungsgemeinschaft. This work was supported by NIH Grants NS39601 and financial support from the Charles H and Anna S Stern foundation and The V-Foundation for cancer Research to CB.

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  1. The Salk Institute for Biological Studies, The Laboratory of Genetics, 10010 N. Torrey Pines Road, La Jolla, 92037, CA, USA

    Kai Treuner, Rob Helton & Carrolee Barlow

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  1. Kai Treuner
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  2. Rob Helton
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  3. Carrolee Barlow
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Correspondence to Carrolee Barlow.

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Treuner, K., Helton, R. & Barlow, C. Loss of Rad52 partially rescues tumorigenesis and T-cell maturation in Atm-deficient mice. Oncogene 23, 4655–4661 (2004). https://doi.org/10.1038/sj.onc.1207604

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