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The Contribution of Insulitis to Diabetes Development in Tumor Necrosis Factor Transgenic Mice

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Transgenic Models of Human Viral and Immunological Disease

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 206))

Abstract

The hallmark of insulin-dependent diabetes mellitus (IDDM) is infiltration in (insulitis) and around (peri-insulitis) the islets of Langerhans, the site of synthesis of insulin (EISENBARTH 1986; GEPTS 1965). Destruction of these islets occurs and, as a consequence, the ability of the patient to produce insulin is eliminated, resulting in frank diabetes. Evidence accumulated over a number of years has shown that IDDM is determined by both genetic and environmental factors. A breakthrough in the genetics was made by the observation of a strong association between IDDM and HLA-DQβ, and later DQα alleles (Todd 1990). These early studies, however, showed clearly that this disease is polygenic in nature, since possession of these HLA susceptibility alleles only predisposed one to, but did not confer a high probability of, IDDM occurrence. In addition, multiple families, including some with identical twins, carrying susceptibility to IDDM have been studied. Strikingly, the results showed that, even when one twin develops IDDM, the probability of the second twin developing disease is only 20%–30%. This has led to the conclusion that environmental effects also play a key role in the development of diabetes (Eisenbarth 1986; Todd 1990).

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Authors and Affiliations

  1. Section of Immunobiology, Yale University School of Medicine, 310 Cedar Street, FMB 412, New Haven, CT, 06520-8011, USA

    R. A. Flavell

  2. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, 06520-8077, USA

    R. A. Flavell

  3. Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, 06520-8034, USA

    A. Kratz & N. H. Ruddle

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Editors and Affiliations

  1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Francis V. Chisari M.D. (Member, Head) (Member, Head)

  2. Division of Experimental Pathology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Francis V. Chisari M.D. (Member, Head) (Member, Head)

  3. Department of Neuropharmacology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Michael B. A. Oldstone M.D. (Member, Head) (Member, Head)

  4. Division of Virology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Michael B. A. Oldstone M.D. (Member, Head) (Member, Head)

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Flavell, R.A., Kratz, A., Ruddle, N.H. (1996). The Contribution of Insulitis to Diabetes Development in Tumor Necrosis Factor Transgenic Mice. In: Chisari, F.V., Oldstone, M.B.A. (eds) Transgenic Models of Human Viral and Immunological Disease. Current Topics in Microbiology and Immunology, vol 206. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85208-4_3

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