title: LEW.1WR1 rats develop autoimmune diabetes spontaneously and in response to environmental perturbation.
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 (RT1(u/u/a)) occurs with a cumulative frequency of approximately 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 beta-cells, whereas alpha- and delta-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.
authors.affiliation: BioMedical Research Models, 67 Millbrook St., Suite 422, Worcester, MA 01606, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Mordes
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Guberski
authors.forename: Jean H
authors.initials: JH
authors.lastname: Leif
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Woda
authors.forename: Joan F
authors.initials: JF
authors.lastname: Flanagan
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.forename: Edward H
authors.initials: EH
authors.lastname: Kislauskis
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Tirabassi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001168:Arthritis / Q000139:chemically induced; D003094:Collagen / Q000633:toxicity; D003920:Diabetes Mellitus / Q000235:genetics* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011070:Poly I-C / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D003094:Collagen; D011070:Poly I-C