Overexpression of bcl-2 in T cells affects insulitis in the nonobese diabetic mouse.
The nonobese diabetic (NOD) mouse is a useful model for human autoimmune diabetes. The gene for the anti-apoptotic protein Bcl-2 has previously been suggested as a probable susceptibility candidate for the NOD mouse disease. In this study, we investigated how overexpression of Bcl-2 in lymphocytes might affect insulitis in NOD mice. A bcl-2 transgene expressed constitutively under the SV40-promoter and the 5'Igh enhancer, Emu, was bred onto NOD background. Two bcl-2 transgenic NOD strains were produced and analysed, one with overexpression of Bcl-2 on only B cells and the other with overexpression of Bcl-2 on both B and T cells. Subsequent to verification of expression pattern and functionality of the transgene, insulitis intensity was investigated in different backcross generations of the two transgenic strains. Overexpression of Bcl-2 on both B and T cells leads to a statistically significant protection of the mice from insulitis compared with normal littermates. Overexpression of Bcl-2 on only B cells, on the other hand, does not have any statistically significant effect on insulitis. Possible mechanisms for the effect of Bcl-2 on insulitis in NOD mice are discussed.
Rietz
C
C
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Screpanti
V
V
Brenden
N
N
Böhme
J
J
Fernández
C
C
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D019254:Genes, bcl-2 / Q000235:genetics* / Q000276:immunology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2