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- Title
CHOP deletion does not impact the development of diabetes but suppresses the early production of insulin autoantibody in the NOD mouse.
- Authors
Satoh, T; Abiru, N; Kobayashi, M; Zhou, H; Nakamura, K; Kuriya, G; Nakamura, H; Nagayama, Y; Kawasaki, E; Yamasaki, H; Yu, L; Eisenbarth, G S; Araki, E; Mori, M; Oyadomari, S; Eguchi, K
- Abstract
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.
- Publication
Apoptosis : an international journal on programmed cell death, 2011, Vol 16, Issue 4, p438
- ISSN
1573-675X
- Publication type
Journal Article
- DOI
10.1007/s10495-011-0576-2