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  • Original Paper
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Expression of Mad1 in T cells leads to reduced thymic cellularity and impaired mitogen-induced proliferation

Oncogene volume 20, pages 1164–1175 (2001)Cite this article

Abstract

To investigate Mad1 function in vivo, transgenic mice were generated that express a Mad1 transgene in T lineage cells under the control of the proximal lck promoter. Thymus size in lck-Mad1 transgenic mice is drastically reduced although representation of the various thymocyte sub populations appears normal. To investigate more closely any effects of Mad1 expression on thymocytes, we examined thymic selection using MHC class I-restricted H-Y-TCR transgenic mice. Mad1 expression in vivo reduces the efficiency of positive selection. Furthermore, thymocytes and splenic T cells from lck-Mad1 transgenic mice display a profound proliferative defect in response to activation with either PMA/Ionomycin or immobilized anti-CD3/CD28 antibody. This proliferative defect is not reversed by addition of exogenous IL-2 and is p53-independent. The growth inhibition caused by Mad1 is overcome by expression of active c-Myc.

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Acknowledgements

We thank T Crafton and her team for excellent support with the animal work. We are grateful to J Bee and G Hutchinson for the help with the IP injections. We would also like to thank D Davies and his team for help with cell sorting and U Knies for technical help during the final phase of the manuscript preparation. We thank D Cantrell for critical reading the manuscript. B Rudolph was supported by a DFG Postdoktoranden Stipendium and a Marie Curie TMR fellowship (ERBFMBICT961770). A-O Hueber was a recipient of a long-term EMBO fellowship. We are grateful for support from the Royal Society and from EC BioTech Grant BIO4-CT96-0052.

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  1. Bettina Rudolph

    Present address: DeveloGen AG, Rudolf-Wissell-Str. 28, Göttingen, D - 37079

  2. Anne-Odile Hueber

    Present address: Centre d'Immunologie, INSERM-CNRS de Marseille-Luminy, Case 906, Marseille, F - 13288, Cedex 9, France

  3. Gerard I Evan

    Present address: UCSF Cancer Center and Cancer Research Institute, 2340 Sutter Street, San Francisco, 94143-0875, California, USA

Authors and Affiliations

  1. Imperial Cancer Research Fund, PO Box 123, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Bettina Rudolph, Anne-Odile Hueber & Gerard I Evan

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Rudolph, B., Hueber, AO. & Evan, G. Expression of Mad1 in T cells leads to reduced thymic cellularity and impaired mitogen-induced proliferation. Oncogene 20, 1164–1175 (2001). https://doi.org/10.1038/sj.onc.1204196

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