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The pro-apoptotic BH3-only protein Bid is dispensable for development of insulitis and diabetes in the non-obese diabetic mouse


Mollah, ZUA; Wali, J; McKenzie, MD; Krishnamurthy, B; Graham, KL; Fynch, S; Szanyi, J; Santamaria, P; Brodnicki, T; Allison, J; Strasser, A; Kay, TWH; Thomas, HE
2011-08
APOPTOSIS
Journal Article
16
8
822-830
Type 1 diabetes is caused by death of insulin-producing pancreatic beta cells. Beta-cell apoptosis induced by FasL may be important in type 1 diabetes in humans and in the non-obese diabetic (NOD) mouse model. Deficiency of the pro-apoptotic BH3-only molecule Bid protects beta cells from FasL-induced apoptosis in vitro. We aimed to test the requirement for Bid, and the significance of Bid-dependent FasL-induced beta-cell apoptosis in type 1 diabetes. We backcrossed Bid-deficient mice, produced by homologous recombination and thus without transgene overexpression, onto a NOD genetic background. Genome-wide single nucleotide polymorphism analysis demonstrated that diabetes-related genetic regions were NOD genotype. Transferred beta cell antigen-specific CD8+ T cells proliferated normally in the pancreatic lymph nodes of Bid-deficient mice. Moreover, Bid-deficient NOD mice developed type 1 diabetes and insulitis similarly to wildtype NOD mice. Our data indicate that beta-cell apoptosis in type 1 diabetes can proceed without Fas-induced killing mediated by the BH3-only protein Bid.
SPRINGER
PANCREATIC BETA-CELLS; ISLET ANTIGENS; NOD MICE; T-CELLS; FAS; EXPRESSION; DEATH; PERFORIN; DESTRUCTION; MECHANISMS
10.1007/s10495-011-0615-z
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Creation Date 2011-08-01 12:00:00