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Prevention of diabetes in non-obese diabetic I-Ak transgenic mice

Nature volume 345, pages 724–726 (1990)Cite this article

Abstract

THE non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) with mononuclear cell infiltration of the islets of Langerhans and selective destruction of the insulin-producing β-cells, as in humans1. Most infiltrating cells are T lymphocytes, and most of these carry the CD4 antigen2. Adoptive transfer of T cells from diabetic NOD mice into irradiated NOD or athymic nude NOD mice induces diabetes3. Susceptibility to IDDM in NOD mice is polygenic4, with one gene linked to the major histocompatibility complex class II locus5, which in NOD mice expresses a unique I-A molecule but no I-E. Speculation exists as to the role of the I-A molecule in the diabetes susceptibility of NOD mice, especially regarding the significance of specific unique residues6,7. To examine the role of the NOD I-A molecule in IDDM pathogenesis, we made NOD/Lt mice transgenic for I-Ak by microinjecting I-Ak α- and β-genes into fertilized NOD/Lt eggs. Insulitis was markedly reduced and diabetes prevented in NOD/Lt mice expressing I-Ak.

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Author notes

  1. Lars Kjer-Nielsen: Department of Pathology and Immunology, Monash University Medical School, Victoria 3181, Australia

Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria, 3050, Australia

    Robyn M. Slattery, Lars Kjer-Nielsen, Janette Allison, Brett Charlton, Thomas E. Mandel & Jacques F. A. P. Miller

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  1. Robyn M. Slattery
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  2. Lars Kjer-Nielsen
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  3. Janette Allison
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  4. Brett Charlton
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  5. Thomas E. Mandel
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  6. Jacques F. A. P. Miller
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Slattery, R., Kjer-Nielsen, L., Allison, J. et al. Prevention of diabetes in non-obese diabetic I-Ak transgenic mice. Nature 345, 724–726 (1990). https://doi.org/10.1038/345724a0

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