EXAMINATION OF OLETF-DERIVED Nidd QTLs BY CONSTRUCTION OF A SERIES OF CONGENIC STRAINS

点击翻译按钮获取中文摘要

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is one of the well-characterized animal models for the study of type II diabetes. Our previous QTL mapping identified 14 loci as candidates for the hyperglycemia in the OLETF rat. Here we generated a series of congenic animals by introgressing into normoglycemic F344 background all 14 OLETF-derived diabetic loci. Subsequent OGTT assay revealed that congenic strains for Nidd1, Nidd2, Nidd3 and Nidd10 showed significantly higher levels of blood glucose in comparison with parental host strain, F344. Furthermore, simultaneously made heterozygote animals for Nidd1, 2 and 10 were normoglycemia, indicating that these loci are recessively inherited. The other nine congenic strains were apparently normoglycemic presumably because the effect of a single locus is too small to be detected by the method employed here. These strains are currently raised on high-fat diet to see if dietary manipulation may help manifest genetic contribution of each locus more clearly. Furthermore, reverse congenic strains whereby F344-derived QTLs are introgressed into OLETF background are also under construction. We believe that these congenic strains should provide useful agents for decomposing complex diabetic traits and for subsequent positional cloning.