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

First Author  Brimnes MK Year  2002
Journal  J Autoimmun Volume  19
Issue  4 Pages  203-13
PubMed ID  12473241 Mgi Jnum  J:80768
Mgi Id  MGI:2447109 Doi  10.1006/jaut.2002.0616
Citation  Brimnes MK, et al. (2002) Low Expression of Insulin in the Thymus of Non-obese Diabetic Mice. J Autoimmun 19(4):203-13
abstractText  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.
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