Low Expression of Insulin in the Thymus of Non-obese Diabetic Mice

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.