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

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Rudolph B,Hueber AO,Evan GI

doi

10.1038/sj.onc.1204196

subject

Has Abstract

pub_date

2001-03-08 00:00:00

pages

1164-75

issue

10

eissn

0950-9232

issn

1476-5594

journal_volume

20

pub_type

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