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. 1988 Jun 1;167(6):1801–1810. doi: 10.1084/jem.167.6.1801

Expression of genetically determined diabetes and insulitis in the nonobese diabetic (NOD) mouse at the level of bone marrow-derived cells. Transfer of diabetes and insulitis to nondiabetic (NOD X B10) F1 mice with bone marrow cells from NOD mice

PMCID: PMC2189678  PMID: 3290380

Abstract

The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is controlled by at least three recessive loci, including one linked to the MHC. To determine whether any of these genetic loci exert their effects via the immune system, radiation bone marrow chimeras were constructed in which (NOD X B10)F1-irradiated recipients were reconstituted with NOD bone marrow cells. Unmanipulated (NOD X B10)F1 mice, or irradiated F1 mice reconstituted with F1 or B10 bone marrow, did not display insulitis or diabetes. In contrast, insulitis was observed in a majority of the NOD----F1 chimeras and diabetes developed in 21% of the mice. These data demonstrate that expression of the diabetic phenotype in the NOD mouse is dependent on NOD-derived hematopoietic stem cells. Diabetogenic genes in the NOD mouse do not appear to function at the level of the insulin-producing beta cells since NOD----F1 chimeras not only developed insulitis and diabetes but also rejected beta cells within pancreas transplants from newborn B10 mice. These data suggest that the beta cells of the NOD mouse do not express a unique antigenic determinant that is the target of the autoimmune response.

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Selected References

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  1. Bendelac A., Carnaud C., Boitard C., Bach J. F. Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells. J Exp Med. 1987 Oct 1;166(4):823–832. doi: 10.1084/jem.166.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  3. Foulis A. K., Liddle C. N., Farquharson M. A., Richmond J. A., Weir R. S. The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom. Diabetologia. 1986 May;29(5):267–274. doi: 10.1007/BF00452061. [DOI] [PubMed] [Google Scholar]
  4. Hattori M., Buse J. B., Jackson R. A., Glimcher L., Dorf M. E., Minami M., Makino S., Moriwaki K., Kuzuya H., Imura H. The NOD mouse: recessive diabetogenic gene in the major histocompatibility complex. Science. 1986 Feb 14;231(4739):733–735. doi: 10.1126/science.3003909. [DOI] [PubMed] [Google Scholar]
  5. Ikehara S., Ohtsuki H., Good R. A., Asamoto H., Nakamura T., Sekita K., Muso E., Tochino Y., Ida T., Kuzuya H. Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7743–7747. doi: 10.1073/pnas.82.22.7743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kanazawa Y., Komeda K., Sato S., Mori S., Akanuma K., Takaku F. Non-obese-diabetic mice: immune mechanisms of pancreatic beta-cell destruction. Diabetologia. 1984 Jul;27 (Suppl):113–115. doi: 10.1007/BF00275663. [DOI] [PubMed] [Google Scholar]
  7. Katz S. I., Tamaki K., Sachs D. H. Epidermal Langerhans cells are derived from cells originating in bone marrow. Nature. 1979 Nov 15;282(5736):324–326. doi: 10.1038/282324a0. [DOI] [PubMed] [Google Scholar]
  8. Koike T., Itoh Y., Ishii T., Ito I., Takabayashi K., Maruyama N., Tomioka H., Yoshida S. Preventive effect of monoclonal anti-L3T4 antibody on development of diabetes in NOD mice. Diabetes. 1987 Apr;36(4):539–541. doi: 10.2337/diab.36.4.539. [DOI] [PubMed] [Google Scholar]
  9. Makino S., Kunimoto K., Muraoka Y., Mizushima Y., Katagiri K., Tochino Y. Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu. 1980 Jan;29(1):1–13. doi: 10.1538/expanim1978.29.1_1. [DOI] [PubMed] [Google Scholar]
  10. Mark C., Figueroa F., Nagy Z. A., Klein J. Cytotoxic monoclonal antibody specific for the Lyt-1.2 antigen. Immunogenetics. 1982;16(1):95–97. doi: 10.1007/BF00364447. [DOI] [PubMed] [Google Scholar]
  11. Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
  12. Miller B. J., Appel M. C., O'Neil J. J., Wicker L. S. Both the Lyt-2+ and L3T4+ T cell subsets are required for the transfer of diabetes in nonobese diabetic mice. J Immunol. 1988 Jan 1;140(1):52–58. [PubMed] [Google Scholar]
  13. Miyazaki A., Hanafusa T., Yamada K., Miyagawa J., Fujino-Kurihara H., Nakajima H., Nonaka K., Tarui S. Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-obese diabetic (NOD) mice: a longitudinal study. Clin Exp Immunol. 1985 Jun;60(3):622–630. [PMC free article] [PubMed] [Google Scholar]
  14. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  15. Ozato K., Mayer N. M., Sachs D. H. Monoclonal antibodies to mouse major histocompatibility complex antigens. Transplantation. 1982 Sep;34(3):113–120. doi: 10.1097/00007890-198209000-00001. [DOI] [PubMed] [Google Scholar]
  16. Prochazka M., Leiter E. H., Serreze D. V., Coleman D. L. Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice. Science. 1987 Jul 17;237(4812):286–289. doi: 10.1126/science.2885918. [DOI] [PubMed] [Google Scholar]
  17. Ron Y., Lo D., Sprent J. T cell specificity in twice-irradiated F1----parent bone marrow chimeras: failure to detect a role for immigrant marrow-derived cells in imprinting intrathymic H-2 restriction. J Immunol. 1986 Sep 15;137(6):1764–1771. [PubMed] [Google Scholar]
  18. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  19. Serreze D. V., Leiter E. H., Worthen S. M., Shultz L. D. NOD marrow stem cells adoptively transfer diabetes to resistant (NOD x NON)F1 mice. Diabetes. 1988 Feb;37(2):252–255. doi: 10.2337/diab.37.2.252. [DOI] [PubMed] [Google Scholar]
  20. Smilek D. E., Boyd H. C., Wilson D. B., Zmijewski C. M., Fitch F. W., McKearn T. J. Monoclonal rat anti-major histocompatibility complex antibodies display specificity for rat, mouse, and human target cells. J Exp Med. 1980 May 1;151(5):1139–1150. doi: 10.1084/jem.151.5.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Terada M., Salzler M., Lennartz K., Mullen Y. The effect of H-2 compatibility on pancreatic beta cell survival in the nonobese diabetic mouse. Transplantation. 1988 Mar;45(3):622–627. doi: 10.1097/00007890-198803000-00024. [DOI] [PubMed] [Google Scholar]
  22. Wicker L. S., Miller B. J., Coker L. Z., McNally S. E., Scott S., Mullen Y., Appel M. C. Genetic control of diabetes and insulitis in the nonobese diabetic (NOD) mouse. J Exp Med. 1987 Jun 1;165(6):1639–1654. doi: 10.1084/jem.165.6.1639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wicker L. S., Miller B. J., Mullen Y. Transfer of autoimmune diabetes mellitus with splenocytes from nonobese diabetic (NOD) mice. Diabetes. 1986 Aug;35(8):855–860. doi: 10.2337/diab.35.8.855. [DOI] [PubMed] [Google Scholar]

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