Finnberg, N., Gruber, J. J., Fei, P. W., Rudolph, D., Bric, A., Kim, S. H., Burns, T. F., Ajuha, H., Page, R., Wu, G. S., Chen, Y. H., McKenna, W. G., Bernhard, E., Lowe, S., Mak, T., El-Deiry, W. S. (March 2005) DR5 knockout mice are compromised in radiation-induced apoptosis. Molecular and Cellular Biology, 25 (5). pp. 2000-2013. ISSN 0270-7306
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 treatment with TRAIL, suggesting that DR5 may be the primary proapoptotic receptor for TRAIL in the mouse. When exposed to ionizing radiation, DR5-nuII 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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | CYTOTOXIC LIGAND TRAIL cytotoxic ligand trail CENTRAL-NERVOUS-SYSTEM central nervous system INDUCED CELL-DEATH induced cell death IN-VIVO in-vivo DEFICIENT MICE deficient mice MOLECULAR-CLONING molecular cloning DECOY RECEPTORS decoy receptors NEURONAL neuronal DEATH death CANCER-CELLS cancer cells P53 |
| Subjects: | diseases & disorders > cancer organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis |
| CSHL Authors: | |
| Communities: | CSHL labs > Lowe lab |
| Depositing User: | CSHL Librarian |
| Date: | March 2005 |
| Date Deposited: | 13 Jan 2012 17:34 |
| Last Modified: | 03 May 2018 16:02 |
| PMCID: | PMC549384 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22568 |
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