Nara Y, Gao M, Ikeda K, Sato T, Sawamura M, Kawano K, Yamori Y
Department of Enviromental Conservation and Development, Kyoto University, Kyoto, 606, Japan.
Biochem Biophys Res Commun. 1997 Dec 8;241(1):200-4. doi: 10.1006/bbrc.1997.7347.
The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese NIDDM. We performed a genome wide scan in F2 progenies obtained by crossing OLETF rats with two control strains, Long-Evans Tokushima Otsuka (LETO) and Fisher-344(F-344) rats. Since diabetes develops only in male progenies, we used only male F2 rats for the linkage studies.Highly significant linkage was observed between the phenotype, postprandial hyperglycemia and P-450ald locus on chromosome 1 and D7Mit 11 locus on chromosome 7. In addition, suggestive linkage was found between fasting glucose level and body weight and these two loci. Four other regions (D1Mit12, D2Mit11, D5Mgh14, and D17Arb1) on chromosome 1, 2, 5, and 17 were detected to influence body weight, fasting glucose level or postprandial hyperglycemia independently. We concluded that non-insulin-dependent diabetes mellitus(NIDDM) in OLETF rats is regulated by multiple genes which affect fasting, postprandial hyperglycemia, and obesity differently.
大冢长-艾氏-德岛肥胖(OLETF)大鼠是肥胖型非胰岛素依赖型糖尿病(NIDDM)的动物模型。我们对通过将OLETF大鼠与两种对照品系,即长-艾氏-德岛大冢(LETO)大鼠和费希尔-344(F-344)大鼠杂交获得的F2代进行了全基因组扫描。由于糖尿病仅在雄性后代中发生,因此我们仅使用雄性F2大鼠进行连锁研究。在1号染色体上的餐后高血糖表型与P-450ald基因座以及7号染色体上的D7Mit 11基因座之间观察到高度显著的连锁。此外,在空腹血糖水平和体重与这两个基因座之间发现了提示性连锁。在1号、2号、5号和17号染色体上的其他四个区域(D1Mit12、D2Mit11、D5Mgh14和D17Arb1)被检测到分别独立影响体重、空腹血糖水平或餐后高血糖。我们得出结论,OLETF大鼠中的非胰岛素依赖型糖尿病(NIDDM)受多个基因调控,这些基因对空腹、餐后高血糖和肥胖的影响各不相同。