OLETF (OTSUKA LONG-EVANS TOKUSHIMA FATTY) RAT - A NEW NIDDM RAT STRAIN

The characteristic features of OLETF rats are: (1) late onset of hyper glycemia (after 18 weeks of age); (2) a chronic course of disease; (3) mild obesity; (4) clinical onset of diabetes mellitus (DM) mostly in males; (5) hereditary trait: (a) multiple recessive genes are involved in the induction of DM; (b) rat MHC, RT1 has no diabetogenic effect; (c) control strain, LETO appears to share some of diabetogenic genes w ith OLETF rats; (d) female OLETF rats also carry diabetogenic genes; a nd (e) one of the diabetogenic genes, designated as odb-1, is transmit ted linked with the X-chromosome of OLETF rats, however testosterone i s an important factor involved in developing diabetes; (6) the changes of pancreatic islets can be classified into three stages: (1) an earl y stage (at less than 9 weeks of age) mild lymphocyte infiltration; (2 ) a hyperplastic stage (10-40 weeks of age); hyperplastic change and f ibrosis in or around islets; (3) a final stage (at more than 40 weeks of age) showing atrophy of islets; (7) diabetic nephropathy; (a) diffu se glomerulosclerosis; (b) nodular lesion (thickening of basement memb ranes, mesangial proliferation, fibrin cap). These clinical and pathol ogic features of disease in OLETF rats resemble those of human NIDDM.