Do the Apoe ^−/− and Ldlr ^−/– Mice Yield the Same Insight on Atherogenesis?

Abstract

Murine models of atherosclerosis are useful for investigating the environmental and genetic influences on lesion formation and composition. Apoe−/− and Ldlr−/− are the two models most extensively used models. The models differ in important ways with respect to the precise mechanism by which their absence enhances atherosclerosis, including differences in plasma lipoproteins. The majority of the gene function studies have utilized only one model, with the results being generalized to atherogenic mechanisms. In only a relatively few cases have studies been conducted in both atherogenic murine models. This review will discuss important differences between the two atherogenic models and will point out studies that have been performed in the two models where results are comparable and those where different results were obtained.

Inhibition of lysophosphatidic acid receptors 1 and 3 attenuates atherosclerosis development in LDL-receptor deficient mice

“…Furthermore, in their study no effect was observed on cholesterol metabolism, whereas we detected a reduction in LDL cholesterol levels. Considering that the above experiments were performed in apoE −/− mice, it is possible that strain specific effects are responsible for the different mechanism observed40. In the past, numerous studies have examined the differences between the LDLr −/− and apoE −/− models.…”

Recommendation on Design, Execution, and Reporting of Animal Atherosclerosis Studies: A Scientific Statement From the American Heart Association

“…34 One of the most commonly used mouse models of atherosclerosis is apoE −/− mice. 35 apoE −/− mice spontaneously develop hypercholesterolemia because of increased chylomicron remnant, very low-density lipoprotein (VLDL) and LDL cholesterol, with total cholesterol concentrations ranging from 300 to 500 mg/dL. 36,37 Although the rate of atherosclerotic lesion development varies greatly between facilities, macrophage foam cells can be present in the aortic root within a month.…”

ATVB Distinguished Scientist Award

“…The comparison of mouse models of atherosclerosis is beyond the scope of this review and has been summarized elsewhere. 104, 105 …”