SPONTANEOUS HYPERCHOLESTEROLEMIA AND ARTERIAL LESIONS IN MICE LACKING APOLIPOPROTEIN-E

被引:1874
|
作者
ZHANG, SH
REDDICK, RL
PIEDRAHITA, JA
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
[3] UNIV N CAROLINA, PROGRAM MOLEC BIOL & BIOTECHNOL, CHAPEL HILL, NC 27599 USA
[4] TEXAS A&M UNIV SYST, DEPT VET ANAT & PUBL HLTH, COLL STN, TX 77840 USA
关键词
D O I
10.1126/science.1411543
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
Apolipoprotein E (apoE) is a ligand for receptors that clear remnants of chylomicrons and very low density lipoproteins. Lack of apoE is, therefore, expected to cause accumulation in plasma of cholesterol-rich remnants whose prolonged circulation should be atherogenic. ApoE-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis. The mutant mice had five times normal plasma cholesterol, and developed foam cell-rich depositions in their proximal aortas by age 3 months. These spontaneous lesions progressed and caused severe occlusion of the coronary artery ostium by 8 months. The severe yet viable phenotype of the mutants should make them valuable for investigating genetic and environmental factors that modify the atherogenic process.
引用
收藏
页码:468 / 471
页数:4
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