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DR5 knockout mice are compromised in radiation-induced apoptosis
Niklas Finnberg1, Joshua J Gruber, Peiwen Fei
1University of Pennsylvania, 415 Curie Blvd., CRB 437, Philadelphia, PA 19104, USA.
Molecular and Cellular Biology
|February 17, 2005
Summary
The death receptor 5 (DR5) knockout mouse develops normally but has an enlarged thymus. DR5 plays an organ-specific role in apoptosis following DNA damage, not during embryogenesis.
Area of Science:
- Cell Biology
- Immunology
- Developmental Biology
Background:
- Death receptor 5 (DR5) induces apoptosis and is a p53 target, but its in vivo function is largely unknown.
- DR5 is a receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
Purpose of the Study:
- To investigate the in vivo role of DR5 in development and adult tissues.
- To understand DR5's function in response to DNA-damaging stimuli.
Main Methods:
- Generated and analyzed DR5 knockout mice.
- Assessed apoptosis in various tissues after ionizing radiation exposure.
- Utilized DR5-null mouse embryo fibroblasts in TRAIL treatment experiments.
Main Results:
- DR5 knockout mice are viable with normal development, except for an enlarged thymus.
- DR5 is not expressed in early embryos but is found in the decidua and chorion.
- DR5-null cells are resistant to TRAIL, indicating DR5 is a primary proapoptotic TRAIL receptor.
- DR5 deficiency reduces apoptosis in thymus, spleen, Peyer's patches, and brain white matter after irradiation.
- A subtle defect in radiation-induced apoptosis was observed in the ileum, colon, and stomach of DR5-null mice.
Conclusions:
- DR5 has a limited role in embryogenesis and early development.
- DR5 plays an organ-specific role in mediating apoptosis in response to DNA damage in adult tissues.