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


CONCLUSIONS
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.
Lenzen
S
S
Institute of Clinical Biochemistry, Hannover Medical School, Germany.
Tiedge
M
M
Elsner
M
M
Lortz
S
S
Weiss
H
H
Jörns
A
A
Klöppel
G
G
Wedekind
D
D
Prokop
C M
CM
Hedrich
H J
HJ
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases; D001402:B-Lymphocytes / Q000473:pathology; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D006029:Glycosuria; D006943:Hyperglycemia; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D007657:Ketone Bodies / Q000652:urine; D007694:Killer Cells, Natural / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D011141:Polyuria; D051381:Rats; D011917:Rats, Inbred Lew; D011922:Rats, Mutant Strains; D013601:T-Lymphocytes / Q000473:pathology
D001786:Blood Glucose; D007328:Insulin; D007657:Ketone Bodies