CHOP deletion does not impact the development of diabetes but suppresses the early production of insulin autoantibody in the NOD mouse
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C/EBP homologous protein (CHOP) has been proposed as a key transcription factor for endoplasmic reticulum (ER) stress-mediated β-cell death induced by inflammatory cytokines in vitro. However, the contribution of CHOP induction to the pathogenesis of type 1 diabetes is not yet clear. To evaluate the relevance of CHOP in the pathogenesis of type 1 diabetes in vivo, we generated CHOP-deficient non-obese diabetic (NOD.Chop−/−) mice. CHOP deficiency did not affect the development of insulitis and diabetes and apoptosis in β-cells. Interestingly, NOD.Chop−/− mice exhibited a delayed appearance of insulin autoantibodies compared to wild-type (wt) mice. Adoptive transfer with the diabetogenic, whole or CD8+-depleted splenocytes induced β-cell apoptosis and the rapid onset of diabetes in the irradiated NOD.Chop−/− recipients with similar kinetics as in wt mice. Expression of ER stress-associated genes was not significantly up-regulated in the islets from NOD.Chop−/− compared to those from wt mice or NOD-scid mice. These findings suggest that CHOP expression is independent of the development of insulitis and diabetes but might affect the early production of insulin autoantibodies in the NOD mouse.