Apoptosis

, Volume 16, Issue 4, pp 438–448

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

  • T. Satoh
  • N. Abiru
  • M. Kobayashi
  • H. Zhou
  • K. Nakamura
  • G. Kuriya
  • H. Nakamura
  • Y. Nagayama
  • E. Kawasaki
  • H. Yamasaki
  • L. Yu
  • G. S. Eisenbarth
  • E. Araki
  • M. Mori
  • S. Oyadomari
  • K. Eguchi
Original Paper
  • 290 Downloads

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.

Keywords

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

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • T. Satoh
    • 1
  • N. Abiru
    • 1
  • M. Kobayashi
    • 1
  • H. Zhou
    • 1
  • K. Nakamura
    • 1
  • G. Kuriya
    • 1
  • H. Nakamura
    • 2
  • Y. Nagayama
    • 3
  • E. Kawasaki
    • 4
  • H. Yamasaki
    • 5
  • L. Yu
    • 6
  • G. S. Eisenbarth
    • 6
  • E. Araki
    • 7
  • M. Mori
    • 8
  • S. Oyadomari
    • 9
  • K. Eguchi
    • 1
    • 2
  1. 1.Department of Endocrinology and Metabolism, Unit of Translational MedicineNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  2. 2.Department of Immunology and Rheumatology, Unit of Translational MedicineNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  3. 3.Department of Medical Gene Technology, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  4. 4.Metabolism/Diabetes and Clinical NutritionNagasaki University HospitalNagasakiJapan
  5. 5.Center for Health and Community MedicineNagasaki UniversityNagasakiJapan
  6. 6.Barbara Davis Center for Childhood DiabetesUCHSCDenverUSA
  7. 7.Department of Metabolic MedicineKumamoto University School of MedicineKumamotoJapan
  8. 8.Laboratory of Molecular GeneticsFaculty of Pharmaceutical Sciences Sojo UniversityKumamotoJapan
  9. 9.Division of Molecular Biology Institute for Genome ResearchThe University of TokushimaTokushimaJapan

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