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Polymorphisms in the Il12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains

Genes & Immunity volume 3, pages 151–157 (2002)Cite this article

Abstract

Interleukin (Il)-12 is a heterodimeric cytokine composed of 35 and 40 kD chains that plays a key role in the induction of Th1 cells, a T cell subset involved in many autoimmune diseases. We report here the cDNA sequence encoding the IL-12 p40 subunit from the autoimmune-prone non-obese diabetic (NOD) mouse, which spontaneously develops type 1 diabetes. Compared with the C57BL/6 sequence, there are two base changes that lead to amino acid replacements. Other autoimmune-prone strains, but not the diabetes-resistant NOR strain, share the same allele as NOD. We found both trans- and cis- allele-dependent effects on levels of basal and induced IL-12p40 expression. Furthermore, we show that one of these changes results in a structural change in the p40 molecule, as evidenced by the failure of a monoclonal antibody to bind NOD IL-12. These findings have implications for the predisposition to autoimmune responses in NOD and other autoimmune-prone mouse strains.

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Authors and Affiliations

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

    S I Ymer, D Huang, K Branson & G Morahan

  2. Roche Milano Ricerche, Via Olgettina 58, Milano, 20132, Italy

    G Penna, S Gregori & L Adorini

Authors
  1. S I Ymer
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  2. D Huang
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  3. G Penna
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  4. S Gregori
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  5. K Branson
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  6. L Adorini
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  7. G Morahan
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Corresponding author

Correspondence to G Morahan.

Additional information

This work was supported by the National Health and Medical Research Council of Australia, by a special Diabetes Interdisciplinary Research Program grant from the NHMRC-Juvenile Diabetes Foundation International and by the CRC for Discovery of Genes for Common Human Diseases.

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Ymer, S., Huang, D., Penna, G. et al. Polymorphisms in the Il12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains. Genes Immun 3, 151–157 (2002). https://doi.org/10.1038/sj.gene.6363849

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  • DOI: https://doi.org/10.1038/sj.gene.6363849

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