Open AccessMarked reduction of high density lipoprotein cholesterol in mice genetically modified to lack apolipoprotein A-I.
Author(s) -
R.C. Williamson,
Denise Lee,
John R. Hagaman,
Nobuyo Maeda
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.15.7134
Subject(s) - apolipoprotein b , medicine , endocrinology , cholesterol , radial immunodiffusion , lipoprotein , high density lipoprotein , apolipoprotein c2 , apolipoprotein e , biology , very low density lipoprotein , immunology , antibody , disease
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.