Williamson R, Lee D, Hagaman J, Maeda N
Department of Pathology and Curriculum in Genetics, University of North Carolina, Chapel Hill 27599-7525.
Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7134-8. doi: 10.1073/pnas.89.15.7134.
Atherosclerosis is a major cause of morbidity and mortality in developed countries. In humans the risk of atherosclerosis is inversely correlated with plasma levels of high density lipoprotein (HDL). As a step in determining whether the experimental reduction of plasma HDL level will increase susceptibility to atherosclerosis, we have used gene targeting in embryonic stem cells to produce mice lacking apolipoprotein A-I, the major protein component of HDL particles. Mice homozygous for the disrupted gene have no plasma apolipoprotein A-I detectable by double immunodiffusion; their total plasma cholesterol and HDL-cholesterol levels after overnight fasting are reduced to about one-third and one-fifth of normal levels, and they are grossly deficient in alpha-migrating HDL particles.
动脉粥样硬化是发达国家发病和死亡的主要原因。在人类中，动脉粥样硬化的风险与血浆高密度脂蛋白（HDL）水平呈负相关。作为确定实验性降低血浆HDL水平是否会增加动脉粥样硬化易感性的一个步骤，我们利用胚胎干细胞中的基因靶向技术培育出了缺乏载脂蛋白A-I（HDL颗粒的主要蛋白质成分）的小鼠。该基因被破坏的纯合子小鼠通过双向免疫扩散法检测不到血浆载脂蛋白A-I；禁食过夜后，它们的总血浆胆固醇和HDL胆固醇水平降至正常水平的约三分之一和五分之一，并且它们严重缺乏α迁移HDL颗粒。
