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

被引:18
作者
Rudolph, B [1 ]
Hueber, AO [1 ]
Evan, GI [1 ]
机构
[1] Imperial Canc Res Fund, London WC2A 3PX, England
关键词
Myc; Mad; oncogene; cell cycle; lymphocyte; tumor suppressor;
D O I
10.1038/sj.onc.1204196
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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/lonomycin 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.
引用
收藏
页码:1164 / 1175
页数:12
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