OLETF (Otsuka Long-Evans Tokushima Fatty) rat: a new NIDDM rat strain

Abstract

The characteristic features of OLETF rats are: (1) late onset of hyperglycemia (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 with OLETF rats; (d) female OLETF rats also carry diabetogenic genes; and (e) one of the diabetogenic genes, designated as odb-1, is transmitted linked with the X-chromosome of OLETF rats, however testosterone is an important factor involved in developing diabetes; (6) the changes of pancreatic islets can be classified into three stages: (1) an early stage (at less than 9 weeks of age) mild lymphocyte infiltration; (2) a hyperplastic stage (10-40 weeks of age); hyperplastic change and fibrosis in or around islets; (3) a final stage (at more than 40 weeks of age) showing atrophy of islets; (7) diabetic nephropathy; (a) diffuse glomerulosclerosis; (b) nodular lesion (thickening of basement membranes, mesangial proliferation, fibrin cap). These clinical and pathologic features of disease in OLETF rats resemble those of human NIDDM.