Low expression of insulin in the thymus of non-obese diabetic mice

Marie K. Brimnes*, Teis Jensen, Trine N. Jørgensen, Birgitte K. Michelsen, Jesper Troelsen, Ole Werdelin

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

Insulin is a predominant autoantigen in IDDM in man and the NOD mouse. Failure of negative selection of diabetogenic T cells in thymus may be an important pre-disposing cause of the disease. To obtain insight into negative selection against such T-cell clones the thymic expression of insulin was studied in NOD and Balb/c mice by quantitative competitive RT-PCR. We detected RNA for insulin in the thymus of 3-week-old Balb/c mice as well as in NOD mice. However, the NOD mice expressed only half as many insulin transcripts as the Balb/c mice. Also, insulin protein was detected in the thymic medulla of both Balb/c and NOD mice. Furthermore, thymic RNA preparations were investigated for the presence of insulin transcription factors. None of the known pancreatic transcription factors for insulin; Pdx-1, Pax6 or Nkx6.1 were detectable in the thymus of Balb/c mice. These results support the idea that low insulin expression in the thymus may be a predisposing cause for development of diabetes in NOD mice analogous with what has been found in humans with the disease-disposing IDDM2 allele. Furthermore, our results suggest that insulin expression in the thymus may be regulated by different principles from those in the pancreas.

Original languageEnglish
JournalJournal of Autoimmunity
Volume19
Issue number4
Pages (from-to)203-213
Number of pages11
ISSN0896-8411
DOIs
Publication statusPublished - Dec 2002
Externally publishedYes

Keywords

  • Autoimmunity
  • Insulin
  • T-cell tolerance
  • Thymus
  • Transcription factors

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