LEW.1WR1 Rats Develop Autoimmune Diabetes Spontaneously and in Response to Environmental Perturbation
Author:
Mordes John P.1, Guberski Dennis L.2, Leif Jean H.1, Woda Bruce A.3, Flanagan Joan F.2, Greiner Dale L.1, Kislauskis Edward H.2, Tirabassi Rebecca S.2
Affiliation:
1. Diabetes Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 2. BioMedical Research Models, Worcester, Massachusetts 3. Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts
Abstract
We describe a new rat model of autoimmune diabetes that arose in a major histocompatibility complex congenic LEW rat. Spontaneous diabetes in LEW.1WR1 rats (RT1u/u/a) occurs with a cumulative frequency of ∼2% at a median age of 59 days. The disease is characterized by hyperglycemia, glycosuria, ketonuria, and polyuria. Both sexes are affected, and islets of acutely diabetic rats are devoid of β-cells, whereas α- and δ-cell populations are spared. The peripheral lymphoid phenotype is normal, including the fraction of ART2+ regulatory T-cells. We tested the hypothesis that the expression of diabetes would be increased by immunological perturbation of innate or adaptive immunity. Treatment of young rats with depleting anti-ART2.1 monoclonal antibody increased the frequency of diabetes to 50%. Treatment with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid increased the frequency of diabetes to 100%. All diabetic rats exhibited end-stage islets. The LEW.1WR1 rat is also susceptible to collagen-induced arthritis but is free of spontaneous thyroiditis. The LEW.1WR1 rat provides a new model for studying autoimmune diabetes and arthritis in an animal with a genetic predisposition to both disorders that can be amplified by environmental perturbation.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Reference47 articles.
1. Green A, Patterson CC, Eurodiab Tiger SG: Trends in the incidence of childhood-onset diabetes in Europe 1989–1998. Diabetologia 44:B3–B8,2001 2. Atkinson MA, Eisenbarth GS: Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221–229,2001 3. Ten S, Kukreja A, Maclaren N: Associations between immune-mediated (type 1) diabetes and other autoimmune diseases. In Diabetes mellitus. A Fundamental and Clinical Text. LeRoith D, Taylor SI, Olefsky JM, Eds. Philadelphia, PA, Lippincott Williams & Wilkins,2004, p.557–574 4. Skyler JS, Brown D, Chase HP, Collier E, Cowie C, Eisenbarth GS, Fradkin J, Grave G, Greenbaum C, Jackson RA, Kaufman FR, Krischer JP, Marks JB, Palmer JP, Ricker A, Schatz DA, Wilson D, Winter WE, Wolfsdorf J, Zeidler A, Dickler H, Eastman RC, Maclaren NK, Malone JI: Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685–1691,2002 5. Lampeter EF, Klinghammer A, Scherbaum WA, Heinze E, Haastert B, Giani G, Kolb H, The DENIS Group: The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. Diabetes 47:980–984,1998
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