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

Author(s): 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;
Details: Publication Year 2011-08,Volume 16,Issue #8,Page 822-830
Journal Title: APOPTOSIS
Publication Type: Journal Article
Abstract: 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.
Publisher: SPRINGER
Keywords: PANCREATIC BETA-CELLS; ISLET ANTIGENS; NOD MICE; T-CELLS; FAS; EXPRESSION; DEATH; PERFORIN; DESTRUCTION; MECHANISMS
Publisher's Version: https://doi.org/10.1007/s10495-011-0615-z
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2011-08-01 12:00:00