AI Article Synopsis
- p53 is a tumor suppressor that plays a crucial role in triggering apoptosis (cell death) through the induction of the Fas receptor, which is significant in autoimmune responses.
- The study examines the effects of removing p53 in mice that already have a Fas defect (lpr mice), hypothesizing that this would worsen their autoimmune symptoms.
- Contrary to expectations, the double mutant mice (lpr with p53 knock-out) exhibited lower autoantibody levels compared to the single mutant lpr mice, suggesting that p53 may have a surprising role in the severity of autoimmune disease.
Article Abstract
The p53 tumor suppressor molecule triggers a key pathway of apoptosis in injured cells, in part through induction of Fas. The importance of Fas as a receptor mediating apoptosis is highlighted by the lupus-like systemic autoimmunity seen in animals and humans with nonfunctional Fas molecules. We set out to see if the absence of p53, superimposed on the Fas defect of lpr mice, might further accelerate or exacerbate their systemic autoimmunity. We generated double mutant mice (p53(-/-) lpr) having defects in both p53- and Fas-dependent pathways, hypothesizing that animals with lesions in both Fas- and p53-dependent pathways would show reduced ability to delete autoreactive or injured cells, thereby producing more severe autoimmune disease. Surprisingly, these mice have lower autoantibody levels than the single mutant lpr mice. These studies suggest an unanticipated role for p53 in the progression of autoimmunity and the production of autoantibodies.
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| http://dx.doi.org/10.1002/eji.200525982 | DOI Listing |
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