{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T07:05:58Z","timestamp":1782025558239,"version":"3.54.5"},"reference-count":47,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,9,1]]},"abstract":"<jats:p>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 \u223c2% 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 \u03b2-cells, whereas \u03b1- and \u03b4-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.<\/jats:p>","DOI":"10.2337\/diabetes.54.9.2727","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2727-2733","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":51,"title":["LEW.1WR1 Rats Develop Autoimmune Diabetes Spontaneously and in Response to Environmental Perturbation"],"prefix":"10.2337","volume":"54","author":[{"given":"John P.","family":"Mordes","sequence":"first","affiliation":[{"name":"Diabetes Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis L.","family":"Guberski","sequence":"additional","affiliation":[{"name":"BioMedical Research Models, Worcester, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean H.","family":"Leif","sequence":"additional","affiliation":[{"name":"Diabetes Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Woda","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan F.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"BioMedical Research Models, Worcester, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale L.","family":"Greiner","sequence":"additional","affiliation":[{"name":"Diabetes Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward H.","family":"Kislauskis","sequence":"additional","affiliation":[{"name":"BioMedical Research Models, Worcester, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca S.","family":"Tirabassi","sequence":"additional","affiliation":[{"name":"BioMedical Research Models, Worcester, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031208151227400_R1","doi-asserted-by":"crossref","unstructured":"Green A, Patterson CC, Eurodiab Tiger SG: Trends in the incidence of childhood-onset diabetes in Europe 1989\u20131998. 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