A DIABETOGENIC GENE (ODB-1) ASSIGNED TO THE X-CHROMOSOME IN OLETF RATS

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat develops hyperglycemia, hyperinsulinemia and mild obesity, features that closely resemble those in human non-insulin-dependent diabetes mellitus (NIDDM). Here, we report a gene involved in the development of diabetes in OLETF rats. Segregation studies using OLETF and an unrelated strain, F344 showed that no diabetes was observed in F1 progeny and less than 12.5% of the F2 progeny developed diabetes, suggesting that multiple recessive genes are involved in the disease. Interestingly, diabetes was observed in approximately 40% of(OLETF female x LETO male)F1 male rats, whereas less than 4% of males were diabetic in the reverse F1 mating, This suggested that the LETO rat which has been established from the same original colony as the OLETF rats shares some, but not all, diabetogenic genes with the OLETF, and that one of the responsible genes locates on the X-chromosome. Linkage study using (OLETF female x F344 male)F2 progeny has confirmed that one of the diabetogenic loci in the OLETF rats locates on the X-chromosome 14 cM distant from the AR gene (LOD = 2.598) and has been designated as ODB-1.