CHOP deletion does not impact the development of diabetes but suppresses the early production of insulin autoantibody in the NOD mouse.

• Satoh, T

• Abiru, Norio

• Kobayashi, M

• Zhou, H

• Nakamura, K

• Kuriya, Genpei

• Nakamura, H

• Nagayama, Y

• Kawasaki, Eiji

• Yamasaki, H

• Yu, L

• Eisenbarth, G S

• Araki, Eiichi

• Mori, M

• Oyadomari, Seiichi

• Eguchi, K

抄録

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.

Apoptosis, 16(4), pp.438-448; 2011

収録刊行物

• Apoptosis : an international journal on programmed cell death

  Apoptosis : an international journal on programmed cell death 16 (4), 438-448, 2011-04

  Springer

キーワード

• Apoptosis
• Autoantibody
• CHOP
• ER stress
• Non-obese diabetic mouse
• Type 1 diabetes

詳細情報

• CRID: 1050568772216313472
• NII論文ID: 120006984789
• NII書誌ID: AA11148723
• ISSN: 13608185
• ISSN: 1573675X
• DOI: 10.1007/s10495-011-0576-2
• HANDLE: 10069/24877
• Web Site: https://nagasaki-u.repo.nii.ac.jp/records/14861
• Web Site: http://link.springer.com/content/pdf/10.1007/s10495-011-0576-2.pdf
• Web Site: http://link.springer.com/article/10.1007/s10495-011-0576-2/fulltext.html
• Web Site: http://link.springer.com/content/pdf/10.1007/s10495-011-0576-2
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN