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

Diabetologia. 2001 Sep;44(9):1189-96. doi: 10.1007/s001250100625.


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.Aa B/Du Cu).

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Autoimmune Diseases*
  • B-Lymphocytes / pathology
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Disease Models, Animal*
  • Glycosuria
  • Hyperglycemia
  • Insulin / blood
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Ketone Bodies / urine
  • Killer Cells, Natural / pathology
  • Macrophages / pathology
  • Male
  • Microscopy, Electron
  • Polyuria
  • Rats
  • Rats, Inbred Lew
  • Rats, Mutant Strains
  • T-Lymphocytes / pathology


  • Blood Glucose
  • Insulin
  • Ketone Bodies