DR5 knockout mice are compromised in radiation-induced apoptosis

Niklas Finnberg, Joshua J. Gruber, Peiwen Fei, Dorothea Rudolph, Anka Bric, Seok Hyun Kim, Timothy F. Burns, Hope Ajuha, Robert Page, Sheng Wu Gen, Youhai Chen, W. Gillies McKenna, Eric Bernhard, Scott Lowe, Tak Mak, Wafik S. El-Deiry

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

DR5 (also called TRAIL receptor 2 and KILLER) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (also called TRAIL and Apo2 ligand). DR5 is a transcriptional target of p53, and its overexpression induces cell death in vitro. However, the in vivo biology of DR5 has remained largely unexplored. To better understand the role of DR5 in development and in adult tissues, we have created a knockout mouse lacking DR5. This mouse is viable and develops normally with the exception of having an enlarged thymus. We show that DR5 is not expressed in developing embryos but is present in the decidua and chorion early in development. DR5-null mouse embryo fibroblasts expressing E1A are resistant to treatmeat with TRAIL, suggesting that DR5 may be the primary proapoptotic receptor for TRAIL in the mouse. When exposed to ionizing radiation, DR5-null tissues exhibit reduced amounts of apoptosis compared to wild-type thymus, spleen, Peyer's patches, and the white matter of the brain. In the ileum, colon, and stomach, DR5 deficiency was associated with a subtle phenotype of radiation-induced cell death. These results indicate that DR5 has a limited role during embryogenesis and early stages of development but plays an organ-specific role in the response to DNA-damaging stimuli.

Original languageEnglish (US)
Pages (from-to)2000-2013
Number of pages14
JournalMolecular and cellular biology
Volume25
Issue number5
DOIs
StatePublished - Mar 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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