The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus

• DOI: 10.1007/s001250100625
• Publication Date: 2002-10-06T10:18:10Z
• Authors: S. Lenzen; M. Tiedge; M. Elsner; S. Lortz; H. Weiss; A. Jörns; G. Klöppel; D. Wedekind; C. -M. Prokop; H. J. Hedrich
• Keywords: Insulitis; Ketonuria; Polyuria; Glycosuria

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.Aa B/Du Cu).The development of diabetes was characterised using biochemical, immunological and morphological methods.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.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.