Genetic background determines the extent of atherosclerosis in ApoE-deficient mice.
Two strains of ApoE-deficient mice were found to have markedly different plasma lipoprotein profiles and susceptibility to atherosclerosis when fed either a low-fat chow or a high-fat Western-type diet. FVB/NJ ApoE-deficient (FVB E0) mice had higher total cholesterol, HDL cholesterol, ApoA1, and ApoA2 levels when compared with C57BL/6J ApoE-deficient (C57 E0) mice. At 16 weeks of age, mean aortic root atherosclerotic lesion area was 7- to 9-fold higher in chow diet-fed C57 E0 mice and 3.5-fold higher in Western diet-fed C57 E0 mice compared with FVB E0 mice fed similar diets. Lesion area in chow diet-fed first-generation mice from a strain intercross was intermediate in size compared with parental values. The distribution of the lesion area in 150 chow diet-fed second-generation progeny spanned the range of the lesion area in both parental strains. There were no correlations between total cholesterol, non-HDL cholesterol, HDL cholesterol, ApoA1, ApoA2, ApoJ, or anti-cardiolipin antibodies and lesion area in the second-generation progeny. Thus, a genomic approach may succeed in identifying the genes responsible for the variation in atherosclerosis susceptibility in these 2 strains of ApoE-deficient mice, which could not be explained by measured plasma parameters.
Dansky
H M
HM
Laboratory of Biochemical Genetics, Rockefeller University, New York, NY 10021, USA.
Charlton
S A
SA
Sikes
J L
JL
Heath
S C
SC
Simantov
R
R
Levin
L F
LF
Shu
P
P
Moore
K J
KJ
Breslow
J L
JL
Smith
J D
JD
D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology; D016633:Apolipoprotein A-II / Q000502:physiology; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001057:Apolipoproteins E; D008074:Lipoproteins; D008075:Lipoproteins, HDL