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

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.