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J Physiol. 2008 Jan 15;586(2):407-17. Epub 2007 Nov 15.

The tumour-suppressor p53 is not required for pancreatic beta cell death during diabetes and upon irradiation.

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  • 1Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.

Abstract

Immune-independent diabetes often occurs via pancreatic beta cell dysfunction. However, the role of the tumour suppressor p53 that regulates cellular life and death in multiple tissues, in pancreatic cell death and diabetes has not been clarified. We have therefore utilized an established mouse model for diabetes in which the MHC class I antigen is overexpressed in pancreatic beta cells under the rat insulin promoter, to investigate the role of p53. We show that pancreatic beta cell death, as determined by TUNEL staining, is elevated in transgenic mice compared to wild-type mice. However, there was no increase in immuno-reactivity towards anti-p53 antibodies in the pancreas of transgenic mice over the course of diabetes formation and beta cell death, suggesting that p53 may not be involved in these processes. Interestingly, p53 expression was also not induced in pancreas upon gamma-irradiation, which resulted in a massive increase in the number of TUNEL-positive cells, suggesting that the p53 pathway may not be causally involved in pancreatic cell death. To further confirm these findings, we generated MHC class I transgenic mice lacking p53 expression. Absence of p53 did not result in any significant changes in pancreatic morphology or affect cell death levels. Importantly, p53 absence did not rescue the diabetic phenotype of the transgenic mice. The results therefore demonstrate that p53 may not be causally involved in pancreatic beta cell death, and suggests that the classical cell death pathway dependent on p53 may not be operating in pancreatic beta cells.

PMID:
18006584
[PubMed - indexed for MEDLINE]
PMCID:
PMC2375583
Free PMC Article
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