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

First Author  Rudolph B Year  2001
Journal  Oncogene Volume  20
Issue  10 Pages  1164-75
PubMed ID  11313860 Mgi Jnum  J:68141
Mgi Id  MGI:1932181 Doi  10.1038/sj.onc.1204196
Citation  Rudolph B, et al. (2001) Expression of Mad1 in T cells leads to reduced thymic cellularity and impaired mitogen-induced proliferation. Oncogene 20(10):1164-75
abstractText  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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