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This Article Full Text Full Text (PDF) All Versions of this Article: 586/2/407    most recent jphysiol.2007.142612v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nam, S. Y. Articles by Sabapathy, K. Search for Related Content PubMed PubMed Citation Articles by Nam, S. Y. Articles by Sabapathy, K. Related Collections Molecular and Genomic

¹ Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore
² Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore

Immune-independent diabetes often occurs via pancreatic β 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 β cells under the rat insulin promoter, to investigate the role of p53. We show that pancreatic β 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 β cell death, suggesting that p53 may not be involved in these processes. Interestingly, p53 expression was also not induced in pancreas upon -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 β cell death, and suggests that the classical cell death pathway dependent on p53 may not be operating in pancreatic β cells.

(Received 7 August 2007; accepted after revision 6 November 2007; first published online 15 November 2007)
Corresponding author K. Sabapathy: Laboratory of Molecular Carcinogenesis, Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore. Email: cmrksb{at}nccs.com.sg