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Direct evidence for the contribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mice

Nature volume 345, pages 722–724 (1990)Cite this article

Abstract

INSULIN-dependent diabetes mellitus is characterized by the infiltration of lymphocytes into the islets of Langerhans of the pancreas (insulitis) followed by destruction of insulin-secreting β-cells leading to overt diabetes1–5. The best model for the disease is the non-obese diabetic (NOD) mouse6,7. Two unusual features of the class II major histocompatibility complex (MHC)8,9 of the NOD mouse are the absence of I-E9 and the presence of unique I-A molecules (I-ANOD)10, in which aspartic acid at position 57 of the β-chain is replaced by serine. This feature is also found in the HLA-DQ chain of many Caucasians with insulin-dependent diabetes mellitus11–13. We have previously reported that the expression of I-E prevents the development of insulitis in NOD mouse14,15. Here we report that the expression of I-Ak (AαkAβk) in transgenic NOD mice can also prevent insulitis, and that this protection is seen not only when the I-A β-chain has aspartic acid as residue 57, but also when this residue is serine. These results show that the single amino-acid substitution at position 57 of the I-A β-chain from aspartic acid to serine is not sufficient for the development of the disease.

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Authors and Affiliations

  1. Institute for Medical Genetics, Kumamoto University Medical School, 4-24-1, Kuhonji, Kumamoto, 862, Japan

    Toru Miyazaki, Masashi Uno, Jun-ichi Miyazaki & Ken-ichi Yamamura

  2. Shionogi Research Laboratories, Shionogi Co. Ltd, Sagisu, Fukushima-ku, Osaka, 553, Japan

    Masahiro Uehira & Hirofumi Nishimoto

  3. Institute for Molecular and Cellular Biology, Osaka University, 1-3, Yamada-oka, Suita, Osaka, 565, Japan

    Hitoshi Kikutani & Tadamitsu Kishimoto

  4. Department of Immunology, Saga Medical School, Sanbonsugi, Oaza, Nabeshima-cho, Saga, 840-01, Japan

    Masao Kimoto

Authors
  1. Toru Miyazaki
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  3. Masahiro Uehira
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  5. Tadamitsu Kishimoto
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  7. Hirofumi Nishimoto
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  8. Jun-ichi Miyazaki
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  9. Ken-ichi Yamamura
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Miyazaki, T., Uno, M., Uehira, M. et al. Direct evidence for the contribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mice. Nature 345, 722–724 (1990). https://doi.org/10.1038/345722a0

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