Su Zhiguang, Li Yuhua, James Jessica C, Matsumoto Alan H, Helm Gregory A, Lusis Aldons J, Shi Weibin
Department of Radiology, University of Virginia, Charlottesville, 22908, USA.
Hum Mol Genet. 2006 May 15;15(10):1650-8. doi: 10.1093/hmg/ddl088. Epub 2006 Apr 4.
Dyslipidemia and hyperglycemia are integral components of the metabolic perturbations in type 2 diabetes. Apolipoprotein E-deficient (apoE(-/-)) mice develop severe hyperlipidemia and significant hyperglycemia when fed a western diet containing 21% fat (w/w), 0.15% cholesterol and 19.5% casein. Using an intercross between C57BL/6J (B6) and C3H/HeJ (C3H) apoE(-/-) mice, we performed quantitative trait locus (QTL) analysis to identify loci contributing to hyperglycemia and associated traits. Fasting plasma levels of glucose, insulin and serum amyloid-P (SAP) and body weight in 234 female F2 mice were measured after being fed the western diet for 12 weeks. QTL analysis revealed one significant QTL, named Bglu3 [95.8 cM, logarithm of odds ratio (OR)(LOD) 4.1], on chromosome 1 and a suggestive QTL on chromosome 9 (38 cM, LOD 2.3) that influenced plasma glucose levels. Bglu3 coincided with loci on distal chromosomal 1 that had a major influence on plasma SAP levels and body weight. Significant correlations between plasma glucose, SAP and body weight were observed in F2 mice. Thus, these results demonstrate genetic linkages of hyperglycemia and body weight with SAP, a marker of the acute-phase response, in hyperlipidemic apoE(-/-) mice and suggest a probability for the Sap gene to be a positional candidate of Bglu3.
血脂异常和高血糖是2型糖尿病代谢紊乱的重要组成部分。载脂蛋白E缺陷（apoE(-/-)）小鼠在喂食含21%脂肪（w/w）、0.15%胆固醇和19.5%酪蛋白的西式饮食时会出现严重的高脂血症和显著的高血糖。利用C57BL/6J（B6）和C3H/HeJ（C3H）apoE(-/-)小鼠的杂交，我们进行了数量性状基因座（QTL）分析，以确定导致高血糖及相关性状的基因座。在喂食西式饮食12周后，测量了234只雌性F2小鼠的空腹血糖、胰岛素和血清淀粉样蛋白-P（SAP）的血浆水平以及体重。QTL分析在1号染色体上发现了一个显著的QTL，命名为Bglu3 [95.8 cM，优势比对数（OR）（LOD）4.1]，在9号染色体上发现了一个暗示性QTL（38 cM，LOD 2.3），它们影响血浆葡萄糖水平。Bglu3与1号染色体远端对血浆SAP水平和体重有主要影响的基因座重合。在F2小鼠中观察到血浆葡萄糖、SAP和体重之间存在显著相关性。因此，这些结果证明了在高脂血症apoE(-/-)小鼠中，高血糖和体重与急性期反应标志物SAP之间存在遗传联系，并提示Sap基因有可能是Bglu3的位置候选基因。
