MARKED REDUCTION OF HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL IN MICE GENETICALLY MODIFIED TO LACK APOLIPOPROTEIN-A-I

被引:181
作者
WILLIAMSON, R
LEE, D
HAGAMAN, J
MAEDA, N
机构
[1] UNIV N CAROLINA, DEPT PATHOL, CHAPEL HILL, NC 27599 USA
[2] UNIV N CAROLINA, CURRICULUM GENET, CHAPEL HILL, NC 27599 USA
关键词
HOMOLOGOUS RECOMBINATION; GENE TARGETING; LIPOPROTEINS;
D O I
10.1073/pnas.89.15.7134
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:7134 / 7138
页数:5
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