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Publication : Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities.

First Author  Valentin-Vega YA Year  2009
Journal  Differentiation Volume  77
Issue  5 Pages  442-9
PubMed ID  19371999 Mgi Jnum  J:149219
Mgi Id  MGI:3848071 Doi  10.1016/j.diff.2009.03.001
Citation  Valentin-Vega YA, et al. (2009) Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities. Differentiation 77(5):442-9
abstractText  Mdm4 is a critical inhibitor of the p53 tumor suppressor. Mdm4 null mice die early during embryogenesis due to increased p53 activity. In this study, we explore the role that Mdm4 plays in the intestinal epithelium by crossing mice carrying the Mdm4 floxed allele to mice with the Villin Cre transgene. Our data show that loss of Mdm4 (Mdm4intDelta) in this tissue resulted in viable animals with no obvious morphological abnormalities. However, these mutants displayed increased p53 levels and apoptosis exclusively in the proliferative compartment of the intestinal epithelium. This phenotype was completely rescued in a p53 null background. Notably, the observed compartmentalized apoptosis in proliferative intestinal epithelial cells was not due to restricted Mdm4 expression in this region. Thus, in this specific cellular context, p53 is negatively regulated by Mdm4 exclusively in highly proliferative cells.
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