Marked reduction of high density lipoprotein cholesterol in mice genetically modified to lack apolipoprotein A-I.
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.
Williamson
R
R
Department of Pathology and Curriculum in Genetics, University of North Carolina, Chapel Hill 27599-7525.
Lee
D
D
Hagaman
J
J
Maeda
N
N
D000818:Animals; D016632:Apolipoprotein A-I / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics; D015139:Blotting, Southern; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002678:Chimera; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D015774:Ganciclovir / Q000494:pharmacology; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010957:Plasmids; D011995:Recombination, Genetic; D015183:Restriction Mapping; D013234:Stem Cells / Q000502:physiology
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D008076:Cholesterol, HDL; D004247:DNA; D002784:Cholesterol; D015774:Ganciclovir