The objectives of this proposal are to develop and characterize a new congenic rat model with spontaneous autoimmune disease. In Phase 1 we will establish a foundation colony of LEW.1WR1 rats and begin genetic crosses to introgress traits from BBDR/Wor and LEW.1WR strains. This should increase the incidence of spontaneous diabetes and may induce spontaneous arthritis and thyroiditis. The incidence and age of onset of type 1 diabetes, and the occurrence of spontaneous arthritis will be monitored. In Phase 2, select Quantitative Trait Loci (QTL) markers will be used to construct speed a congenic strain with a high incidence of multiple spontaneous autoimmune disorders. Some 5 percent of the U.S. population is affected by one or more autoimmune diseases. Experimental animal models facilitate the study of the pathogenesis of autoimmune diseases and permit the evaluation of treatment protocols that are not immediately feasible or ethical in humans. Animal models also provide populations of genetically uniform subjects that can be maintained under environmentally controlled conditions. It is our expectation that this new model of autoimmunity will expedite the development of safe and effective pharmaceutical agents for the treatment of Rheumatoid Arthritis, Type 1 Diabetes, and Hashimoto's Thyroiditis.
This research effort will result in a new characterized model of autoimmune diseases. The animal model will generate income by direct sales and contract research within the 15,000 sq. ft. BRM facility.
| Tirabassi, Rebecca S; Guberski, Dennis L; Blankenhorn, Elizabeth P et al. (2010) Infection with viruses from several families triggers autoimmune diabetes in LEW*1WR1 rats: prevention of diabetes by maternal immunization. Diabetes 59:110-8 |
| Blankenhorn, Elizabeth P; Cort, Laura; Greiner, Dale L et al. (2009) Virus-induced autoimmune diabetes in the LEW.1WR1 rat requires Iddm14 and a genetic locus proximal to the major histocompatibility complex. Diabetes 58:2930-8 |
| Mordes, John P; Guberski, Dennis L; Leif, Jean H et al. (2005) LEW.1WR1 rats develop autoimmune diabetes spontaneously and in response to environmental perturbation. Diabetes 54:2727-33 |
