OLETF x（OLETF x 费希尔344）回交大鼠脂质代谢定量性状基因座的研究

Quantitative trait loci for lipid metabolism in the study of OLETF x (OLETF x Fischer 344) backcross rats.

作者信息

Yamasaki Y, Watanabe T K, Okuno S, Ono T, Oga K, Mizoguchi-Miyakita A, Goto Y, Shinomiya H, Momota H, Miyao H, Hayashi I, Asai T, Suzuki M, Harada Y, Hishigaki H, Wakitani S, Takagi T, Nakamura Y, Tanigami A

机构信息

Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan.

出版信息

Clin Exp Pharmacol Physiol. 2000 Nov;27(11):881-6. doi: 10.1046/j.1440-1681.2000.03353.x.

DOI:10.1046/j.1440-1681.2000.03353.x

PMID:11071303

Abstract

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a model of type II diabetes with accompanying dyslipidaemia and obesity. 2. To define chromosomal intervals associated with obesity (abdominal fat weight and plasma leptin levels), dyslipidaemia (plasma triglyceride, cholesterol and free fatty acids) and hyperglycaemia (plasma glucose levels), we have performed genome-wide quantitative traits loci (QTL) analyses of 115 male OLETF x (OLETF x Fischer 344) backcross animals at 16 weeks of age. 3. The Diabetes Mellitus OLETF type I (Dmo1) locus on rat chromosome 1 showed statistically significant involvement in elevations of plasma levels of triglycerides (P = 4.87 x 10(-6) at D1Rat90) and total cholesterol (P = 1.16 x 10(-5) at D1Rat306). 4. No other loci produced significant linkage to these observed phenotypes. 5. These analyses have confirmed the importance of Dmo1 in lipid homeostasis at younger ages as well as during overt diabetes, which appears later. Thus, alterations at the Dmo1 locus are a major risk factor for pathogenesis in the strain, a finding that agrees with physiological studies that indicate a role for dyslipidaemia in the type II diabetic syndrome of OLETF rats.

摘要

大冢长-伊原-德岛肥胖（OLETF）大鼠是一种伴有血脂异常和肥胖的II型糖尿病模型。2. 为了确定与肥胖（腹部脂肪重量和血浆瘦素水平）、血脂异常（血浆甘油三酯、胆固醇和游离脂肪酸）以及高血糖（血浆葡萄糖水平）相关的染色体区间，我们对115只16周龄的雄性OLETF×（OLETF×费希尔344）回交动物进行了全基因组数量性状位点（QTL）分析。3. 大鼠1号染色体上的糖尿病OLETF I型（Dmo1）位点在统计学上显著参与了血浆甘油三酯水平的升高（在D1Rat90处P = 4.87×10⁻⁶）和总胆固醇水平的升高（在D1Rat306处P = 1.16×10⁻⁵）。4. 没有其他位点与这些观察到的表型产生显著连锁。5. 这些分析证实了Dmo1在较年轻时以及明显糖尿病发生后期的脂质稳态中的重要性。因此，Dmo1位点的改变是该品系发病机制的一个主要危险因素，这一发现与生理学研究一致，生理学研究表明血脂异常在OLETF大鼠的II型糖尿病综合征中起作用。