Transgenic animal models for type 1 diabetes: linking a tetracycline-inducible promoter with a virus-inducible mouse model.
Autoimmunity is thought to emerge as a consequence of genetic predispositions and environmental tiggering factors. Often the etiology and the mechanisms involved in the autoaggressive destruction of self-components are rather complex and in many cases poorly understood. Chemokines and cytokines are central mediators of inflammatory processes that are involved in initiation and progression of autoimmunity. Many animal models for human autoimmune diseases use transgenic technology to express chemokines and/or cytokines in an organ or tissue specific manner. However, most of these model systems express the transgene irreversibly without considering the time of expression as a very important parameter. Here, we review experiences that were made from using a tetracycline-inducible promotor system (tTA-system) to express TNFalpha at various times during an ongoing autoimmune process, such as the destruction of pancreatic beta-cells in a mouse model for human type 1 diabetes.
Christen
Urs
U
Department of Immune Regulation, IR-3, La Jolla Institute for Allergy and Immunology, San Diego, CA, USA.
von Herrath
Matthias G
MG
D000818:Animals; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000187:drug effects; D013752:Tetracycline / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014777:Virus Diseases / Q000150:complications
D014409:Tumor Necrosis Factor-alpha; D013752:Tetracycline