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The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus
Authors:Lenzen S  Tiedge M  Elsner M  Lortz S  Weiss H  Jörns A  Klöppel G  Wedekind D  Prokop C M  Hedrich H J
Affiliation:(1) Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany, DE;(2) Centre of Anatomy, Hannover Medical School, Hannover, Germany, DE;(3) Institute of Pathology, University of Kiel, Kiel, Germany, DE;(4) Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany, DE
Abstract:Aims/hypothesis: We describe a new Type I (insulin-dependent) diabetes mellitus rat model (LEW.1AR1/Ztm-iddm) which arose through a spontaneous mutation in a congenic Lewis rat strain with a defined MHC haplotype (RT1.A a B/D u C u ). Methods: The development of diabetes was characterised using biochemical, immunological and morphological methods. Results: Diabetes appeared in the rats with an incidence of 20 % without major sex preference at 58 ± 2 days. The disease was characterised by hyperglycaemia, glycosuria, ketonuria and polyuria. In peripheral blood, the proportion of T lymphocytes was in the normal range expressing the RT6.1 differentiation antigen. Islets were heavily infiltrated with B and T lymphocytes, macrophages and NK cells with beta cells rapidly destroyed through apoptosis in areas of insulitis. Conclusion/interpretation: This Type I diabetic rat develops a spontaneous insulin-dependent autoimmune diabetes through beta cell apoptosis. It could prove to be a valuable new animal model for clarifying the mechanisms involved in the development of autoimmune diabetes. [Diabetologia (2001) 44: 1189–1196] Received: 6 December 2000 and in revised form: 28 May 2001
Keywords:Type I diabetes mellitus   animal model   rat   apoptosis.
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