Genetic Analysis of Diabetes in a Spontaneously Diabetic Non-obese Torii Rat, a Newly Established Animal Model

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A spontaneously diabetic Torii (SDT) rat is an animal model for type 2 diabetes with non-obese in humans. A cumulative incidence of diabetes of 100% was noted by 30weeks of age in male rats, while it was only 33.3% even by 65 weeks of age in the female rats (Int.J Exp Diab Res, 1 : 89-100, 2000). We performed pathological and physiological characterizations and QTL analysis using a backcross panel {(BN x SDT) F1 x SDT}. All of the F1 progenies showed no sign of glucose intolerance at 20 weeks of age and hyperglycemia at 25 weeks of age. Only 27 rats (8.5%) out of 319 male backcrosses showed glucose intolerance at 20 weeks of age or hyperglcemia at 25 weeks of age. By the first genome-wide scan for responsible genes in this strain using SSLP markers, we mapped five QTLs for glucose intolerance ; these were Niddm/sdt 1, Niddm/sdt2, Niddm/sdt3, Niddm/sdt4, and Niddm/sdt5 on chromosomes 1, 2, 11, 18 and X, respectively. They were mapped on chromosomal regions that were not homologous to human diabetes-susceptibility loci already reported. For these QTLs, prevalence of SDT alleles significantly exacerbated glucose intolerance. Furthermore, a synergistic interaction among these QTLs contributed to the onset of glucose intolerance. These genetic loci are responsible for glucose intolerance in the SDT rat.