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

Oncogene
B RudolphGerard Evan

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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Citations

May 3, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jidong ZhuJunying Yuan
Sep 26, 2007·Molecular and Cellular Biology·Jun-Soo YunElva Díaz
Mar 2, 2006·Molecular and Cellular Biology·Shala DezfouliPeter J Hurlin
Apr 16, 2014·Biochimica Et Biophysica Acta·Jason M Link, Peter J Hurlin
May 27, 2014·Biochimica Et Biophysica Acta·Daniel DiolaitiRobert N Eisenman
Sep 15, 2004·International Review of Cytology·Peter J Hurlin, Shala Dezfouli
Jun 11, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Vimal SelvarajPaul S Cooke
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rodney A PrellAndrew D Weinberg
Jan 18, 2006·Journal of Cell Science·C William Hooker, Peter J Hurlin

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