Transgenic overexpression of human Bcl-2 in islet beta cells inhibits apoptosis but does not prevent autoimmune destruction.
Insulin-dependent diabetes mellitus results when > 90% of the insulin-producing beta cells in the pancreatic islets are killed as a result of autoimmune attack by T cells. During the progression to diabetes, islet beta cells die as a result of different insults from the immune system. Agents such as perforin and granzymes, CD95 ligand and tumor necrosis factor-alpha, or cytokines and free-radicals have all been shown to cause beta cell apoptosis. The anti-apoptotic protein, Bcl-2, might protect against some of these stimuli. We have therefore generated transgenic mice expressing human Bcl-2 in their islet beta cells. Although Bcl-2 was able to prevent apoptosis induced by cytotoxic agents against beta cells in vitro, Bcl-2 alone could not prevent or ameliorate cytotoxic or autoimmune beta cell damage in vivo.
Allison
J
J
The Walter and Eliza Hall Institute for Medical Research, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia.
Thomas
H
H
Beck
D
D
Brady
J L
JL
Lew
A M
AM
Elefanty
A
A
Kosaka
H
H
Kay
T W
TW
Huang
D C
DC
Strasser
A
A
D017668:Age of Onset; D000818:Animals; D017209:Apoptosis; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000276:immunology*; D004195:Disease Models, Animal; D004351:Drug Resistance; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D019311:Staurosporine / Q000494:pharmacology; D013311:Streptozocin / Q000494:pharmacology
D018122:B7-1 Antigen; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D013311:Streptozocin; D019311:Staurosporine