Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma.
We have produced transgenic mouse strains harboring class II major histocompatibility complex or interferon-gamma genes linked to the human insulin promoter. These experiments were designed to investigate the consequences of the expression of immunological effector molecules by nonimmunological cells. In both of these studies we observed the disappearance from the pancreas of the insulin-producing beta cells coinciding with the development of insulin-dependent diabetes mellitus. Transgenic mice expressing both chains of the I-A gene showed progressive atrophy of the islets of Langerhans, whereas mice expressing interferon-gamma suffered an inflammatory destruction of the islets.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004274:DNA, Recombinant; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006029:Glycosuria / Q000652:urine; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000032:analysis / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics*; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010179:Pancreas / Q000032:analysis; D010375:Pedigree; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics
D001786:Blood Glucose; D004274:DNA, Recombinant; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D012333:RNA, Messenger; D012313:RNA; D007371:Interferon-gamma