Genetic loci determining bone density in mice with diet-induced atherosclerosis
Genetic loci determining bone density in mice with diet-induced atherosclerosis
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DOI：
10.1152/physiolgenomics.2001.5.4.205
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发表时间：
2001-04-27
影响因子：
4.6
通讯作者：
Lusis, AJ
中科院分区：
文献类型：
--
作者：
Drake, TA;Schadt, E;Lusis, AJ
这项研究调查了饮食诱导的动脉粥样硬化小鼠的骨密度相关性状与脂肪组织和血脂之间的表型和遗传关系。对16个月龄的雌性C57BL/6J和DBA/2J杂交后代进行了4个月的动脉粥样硬化饲料喂养，用计算机断层摄影和放射学方法对其股骨骨质量、密度和生物力学性能进行多项测量。此外，还评估了体重和身长、脂肪组织质量、血脂和胰岛素以及主动脉脂肪损害。骨量与动脉粥样硬化的程度和促氧化脂质水平呈负相关，与体重、身长和脂肪组织质量直接相关。利用复合区间作图(CIM)和多性状分析进行QTL分析，确定了6个具有多性状CIM LOD评分的基因座，其中3个与脂肪组织和血浆高密度脂蛋白连锁。应用统计检验区分紧密连锁和多效性，支持其中两个基因座对这些性状存在潜在的多效性效应。这项研究表明，患动脉粥样硬化的老年雌性小鼠的骨量具有多个遗传决定因素，并提供了将骨密度的调节与脂肪组织和血脂联系起来的表型和遗传学证据。
This study investigates the phenotypic and genetic relationships among bone-density-related traits and those of adipose tissue and plasma lipids in mice with diet-induced atherosclerosis. Sixteen-month-old female F2 progeny of a C57BL/6J and DBA/2J intercross, which had received an atherogenic diet for 4 mo, were examined for multiple measures of femoral bone mass, density, and biomechanical properties using both computerized tomographic and radiographic methods. In addition, body weight and length, adipose tissue mass, plasma lipids and insulin, and aortic fatty lesions were assessed. Bone mass was inversely correlated with extent of atherosclerosis and with a prooxidant lipid profile and directly correlated with body weight, length, and, most strongly, adipose tissue mass. Quantitative trait locus (QTL) analysis, using composite interval mapping (CIM) and multi-trait analysis, identified six loci with multitrait CIM LOD scores > 5. Three of these coincided with loci linked with adipose tissue and plasma high-density lipoprotein. Application of statistical tests for distinguishing close linkage vs. pleiotropy supported the presence of a potential pleiotropic effect of two of the loci on these traits. This study shows that bone mass in older female mice with atherosclerosis has multiple genetic determinants and provides phenotypic and genetic evidence linking the regulation of bone density with adipose tissue and plasma lipids.