Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/lty/Bcg genes on chromosome 1 (original) (raw)

Nature volume 353, pages 262–265 (1991) Cite this article

Abstract

HUMAN type 1 (insulin-dependent) diabetes is a common autoimmune disease of the insulin-producing β cells of the pancreas which is caused by both genetic and environmental factors1,2. Several features of the genetics and immunopathology of diabetes in nonobese diabetic (NOD) mice are shared with the human disease1,3,4. Of the three diabetes-susceptibility genes, Idd-1 (refs 5–7), -3 and -4 (ref. 4) that have been mapped in mice to date, only in the case of Idd-1 is there any evidence for the identity of the gene product: allelic variation within the murine immune response /-A/3 gene and its human homologue HLA-DQB1 correlates with susceptibility, implying that I–Aβ is a component of Idd-1 (refs 5–11). We report here the mapping of Idd-5 to the proximal region of mouse chromosome 1. This region contains at least two candidate susceptibility genes, the interleukin-1 receptor gene (Il-lrl; ref. 12) and Lsh/Ity/Bcg (refs 13-19), which encodes resistance to bacterial and parasitic infections and affects the function of macrophages.

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References

  1. Castano, L. & Eisenbarth, G. S. A. Rev. Immun. 8, 647–679 (1990).
    Article CAS Google Scholar
  2. Risch, N. Am. J. hum. Genet. 40, 1–14 (1987).
    CAS PubMed PubMed Central Google Scholar
  3. Makino, S. et al. Expl Anim. 29, 1–13 (1980).
    Article CAS Google Scholar
  4. Todd, J. A. et al. Nature 351, 542–547 (1991).
    Article ADS CAS PubMed Google Scholar
  5. Hattori, M. et al. Science 231, 733–735 (1986).
    Article ADS CAS PubMed Google Scholar
  6. Prochazka, M., Leiter, E. H., Serreze, D. V. & Coleman, D. L. Science 237, 286–289 (1987).
    Article ADS CAS PubMed Google Scholar
  7. Wicker, L. S. et al. J. exp. Med. 165, 1639–1654 (1987).
    Article CAS PubMed Google Scholar
  8. Todd, J. A., Bell, J. I. & McDevitt, H. O. Nature 329, 599–604 (1987).
    Article ADS CAS PubMed Google Scholar
  9. Miyazaki, T. et al. Nature 345, 722–724 (1990).
    Article ADS CAS PubMed Google Scholar
  10. Slattery, R. M. et al. Nature 345, 724–726 (1990).
    Article ADS CAS PubMed Google Scholar
  11. Lund, T. et al. Nature 345, 727–729 (1990).
    Article ADS CAS PubMed Google Scholar
  12. Copeland, N. G. et al. Genomics 9, 44–50 (1991).
    Article CAS PubMed Google Scholar
  13. Blackwell, J. M. et al. Immun. Lett. (in the press).
  14. Schurr, E. et al. Immun. Today 12, 42–45 (1991).
    Article Google Scholar
  15. Skamene, E. et al. Nature 297, 506–509 (1982).
    Article ADS CAS PubMed Google Scholar
  16. Malo, D. et al. Genomics 10, 356–364 (1991).
    Article CAS PubMed Google Scholar
  17. Mock, B. et al. Genomics 7, 57–64 (1990).
    Article CAS PubMed Google Scholar
  18. Hillyard, A. L., Doolittle, D. P., Davisson, M. T. & Roderick, T. H. Locus Map of the Mouse with Comparative Points of Human on Mouse (Jackson Laboratory, Barbor, Maine, 1991).
    Google Scholar
  19. Hutchings, P. et al. Nature 348, 639–642 (1990).
    Article ADS CAS PubMed Google Scholar
  20. Harada, M. & Makino, S. Diabetologia 27, 604–606 (1984).
    Article CAS PubMed Google Scholar
  21. Yasunami, R. & Bach, J.-F. Eur. J. Immun. 18, 481–484 (1988).
    Article CAS Google Scholar
  22. Wicker, L. S., DeLarato, N. H., Pressey, A. & Peterson, L. B. in Proc. P & S Biomed. Sci. Symp.; Molecular Mechanisms of Immunological Self-recognition (eds Vogel, H. J. & Alt, S. W.) (Academic, New York, in the press).
  23. Wicker, L. S., DeLareto, N. H., Pressey, A. & Peterson, L. B. in Frontiers in Diabetes Research II: Lessons from Animal Diabetes III (ed. Shafrir, E.) 67–72 (Smith-Gordon, London, 1991).
    Google Scholar
  24. Jacob, C. O., Aiso, S., Michie, S. & McDevitt, H. O. Proc. natn. Acad. Sci. U.S.A. 87, 968–972 (1990).
    Article ADS CAS Google Scholar
  25. Mandrup-Poulsen, T. et al. Curr. Topics Microbial. Immun. 164, 169–193 (1990).
    CAS Google Scholar
  26. Sims, J. E. et al. Science 241, 585–589 (1988).
    Article ADS CAS PubMed Google Scholar
  27. Love, J. M., Knight, A. M., McAleer, M. A. & Todd, J. A. Nucleic Acids Res. 18, 4123–4130 (1990).
    Article CAS PubMed PubMed Central Google Scholar
  28. Cornall, R. J., Aitman, T. J., Hearne, C. M. & Todd, J. A. Genomics 10, 874–881 (1991).
    Article CAS PubMed Google Scholar
  29. Hearne, C. M. et al. Mamm. Genome 1, 273–282 (1991).
    Article CAS PubMed Google Scholar
  30. Hogarth, P. M. et al. J. Immun. 146, 369–377 (1991).
    CAS PubMed Google Scholar

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Author notes

  1. Alison Pressey, Nicole H. DeLarato and Linda S. Wicker: Autoimmune Diseases Research, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065, USA
  2. Laurence B. Peterson: Department of Cellular and Molecular Pharmacology, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065, USA

Authors and Affiliations

  1. Nuffield Department of Surgery, John Radcliffe Hospital, Headington, Oxford, 0X3 9DU, UK
    Richard J. Cornall, Jan-Bas Prins, John A. Todd, Alison Pressey, Nicole H. DeLarato, Linda S. Wicker & Laurence B. Peterson

Authors

  1. Richard J. Cornall
  2. Jan-Bas Prins
  3. John A. Todd
  4. Alison Pressey
  5. Nicole H. DeLarato
  6. Linda S. Wicker
  7. Laurence B. Peterson

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Cornall, R., Prins, JB., Todd, J. et al. Type 1 diabetes in mice is linked to the _interleukin_-1 receptor and Lsh/lty/Bcg genes on chromosome 1.Nature 353, 262–265 (1991). https://doi.org/10.1038/353262a0

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