Lack of apoA-I is not associated with increased susceptibility to atherosclerosis in mice.
The consequences of the lack of apolipoprotein A-I (apoA-I) were evaluated in mice made to lack apoA-I by gene targeting. Inbred strain 129 mice homozygous for the inactive Apoa1 gene and maintained on regular mouse chow had markedly reduced total cholesterol (26% normal) and high-density lipoprotein (HDL) cholesterol (25% normal) levels in their plasma. Their plasma lipoproteins lacked apoA-I and were reduced in all other apolipoproteins but apoE. ApoE comprises about one third of the protein of HDL particles in homozygotes, whereas it is present in only trace amounts in normal HDL. Despite the reduction of HDL cholesterol, no atherosclerotic lesions were observed in any of the homozygous mice evaluated (up to 15 months of age). After being maintained on an atherogenic diet for 4 weeks, total plasma cholesterol of the homozygous mutants increased by 20 mg/dL, while that of normals increased by 60 mg/dL. Mice with mixed 129 and C57BL/6J genetic backgrounds were fed the atherogenic diet for 20 weeks. A small number of foam cells were found attached to the aortic surface in some of the animals, but the extent and occurrence of these depositions were not related to the apoA-I genotype. Our results demonstrate that a lack of apoA-I does not by itself cause atherosclerosis in mice.
Li
H
H
Department of Pathology, University of North Carolina, Chapel Hill 27599-7525.
Reddick
R L
RL
Maeda
N
N
D000818:Animals; D001011:Aorta / Q000473:pathology; D016632:Apolipoprotein A-I / Q000172:deficiency* / Q000235:genetics; D001053:Apolipoproteins / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood* / Q000235:genetics / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004036:Diet, Atherogenic; D004198:Disease Susceptibility; D005487:Foam Cells / Q000473:pathology; D006720:Homozygote; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008055:Lipids; D002784:Cholesterol