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

S Lenzen, M Tiedge, M Elsner, S Lortz, H Weiss… - Diabetologia, 2001 - Springer
S Lenzen, M Tiedge, M Elsner, S Lortz, H Weiss, A Jörns, G Klöppel, D Wedekind…
Diabetologia, 2001Springer
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 …
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]
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