Multifactorial control of autoimmune insulin-dependent diabetes in NOD mice: lessons for inflammatory bowel disease

  • E. H. Leiter

Abstract

The mouse has been a favored organism for development of models of human genetic diseases. The mouse genome is over 85% homologous with the human genome. In contrast to the other nonhuman mammalian genomes, the mouse genome has been extensively characterized, and is readily amenable to manipulation by transgenic or gene targeting technologies. Inbred mice have been extensively employed to analyze the complex interplay between genes and environment in the development and control of immune responsiveness to antigens. A multiplicity of genes with known effects on immune responsiveness have been mapped. The use of gene targeting to elicit null mutations in specific interleukin genes (e.g. I12, I14, I110, Tgfb1)or T cell receptor (TCR) genes render mice susceptible to intestinal inflammation. Indeed, in certain of these gene ‘knockout’ mice, mucosal inflammation is often the most profound lesion observed; perhaps because, unlike internal tissues, mucosal epithelium and attendant gut-associated lymphoreticular tissue (GALT) are under constant antigenic bombardment1. Cytokine imbalances elicited by targeting specific interleukin genes may lead to loss of T lymphocyte-mediated suppression of B lymphocyte responses to mucosal antigens1. Differential sensitivity of certain inbred strains to colonic inflammation induced by the macrophage-activating agent, dextran sulfate2, affords a promising avenue for identifying major genes associated with acute inflammatory responsiveness leading to ulceration of the lower bowel. In addition, identification of a spontaneous, juvenile-onset colitis in C3H/HeJBir mice3 affords yet another promising tool for dissecting the complex relationship between genes and environment that must underlie most instances of inflammatory bowel disease (IBD) in humans.

Keywords

Inflammatory Bowel Disease Major Histocompatibility Complex Major Histocompatibility Complex Class Insulin Dependent Diabetes Mellitus Glutamic Acid Decarboxylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers and Axcan Pharma, Inc. 1994

Authors and Affiliations

  • E. H. Leiter

There are no affiliations available

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