LEW.1WR1 Rats Develop Autoimmune Diabetes Spontaneously and in Response to Environmental Perturbation

  1. John P. Mordes1,
  2. Dennis L. Guberski2,
  3. Jean H. Leif1,
  4. Bruce A. Woda3,
  5. Joan F. Flanagan2,
  6. Dale L. Greiner1,
  7. Edward H. Kislauskis2 and
  8. Rebecca S. Tirabassi2
  1. 1Diabetes Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
  2. 2BioMedical Research Models, Worcester, Massachusetts
  3. 3Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts
  1. Address correspondence and reprint requests to Dennis L. Guberski, BioMedical Research Models, 67 Millbrook St., Suite 422, Worcester, MA 01606. E-mail: dguberski{at}biomere.com


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.


  • The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

    Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

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    • Accepted June 3, 2005.
    • Received March 1, 2005.
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