There are well-known genetic background effects on atherosclerosis susceptibility in mice. To study the basis of these effects, we have generated the apolipoprotein E-null mutation in mouse embryonic stem cells of 129/SvEv origin, maintained it in the inbred strain (129-apoE), and compared these mice with those previously made in strain 129/Ola and backcrossed to a C57BL/6 genetic background (B6-apoE). Plasma cholesterol and triglyceride levels in the apoE-129 mice are twice the levels in apoE-B6, and both VLDL/chylomicron remnants and HDL particles are increased. Regression analysis of plaque size relative to the age of mice suggests that the initiation of atherosclerotic plaque development at the aortic root is slower in 129-apoE mice (intercept at 3.9 months in females and 4.1 months in males) than in B6-apoE mice (1.3 months in females and 2.8 months in males). In contrast, 129-apoE mice develop extensive plaques in the aortic arches earlier than B6-apoE mice. Distinct differences in the geometry of the aortic arch between the two strains suggest that anatomical differences may contribute to the effects of genetic background on atherosclerosis. The 129-apoE/B6-apoE pair thus provides a tool to study factors governing the relation between arterial geometry and the location of plaque development.
|Number of pages
|Published - Nov 2007
Bibliographical noteFunding Information:
We thank Joshua Knowles, Jeffrey Hodgin, Yau-Sheng Tsai, Goeffrey Lewis, and Mathew Alexander for making their data available for analyses, Svetlana Zhilicheva and Jennifer Wilder, Kimberly Kluckman and Annette Staton for expert technical assistance. We thank Drs. Oliver Smithies and Byron Ballou for useful comments. This work was supported by HL-42630 from the National Institutes of Health.
- Animal model
- Aortic arch
- Aortic root
- Atherosclerotic plaque distribution
- Ductus arteriosus
- Inbred mouse strain
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine