Abstract 13783: High Density Lipoprotein Profile of ApolipoproteinE Knocked Out Mice
Objective: Although the apolipoproteinE knocked out (apoE) -/- mouse is by far the most used animal model in cardiovascular research, there is very little information available about the HDL subpopulation profile of these animals. Here, we attempt to define the HDL profile of apoE-/- mice in reference to apoAI, apoAII, apoAIV and apoE and compare it to that of wild-type mice.
Methods and Results: HDL subpopulations of 16 apoE-/- mice of C57BL background and 6 C57BL apoE+/+ mice were investigated. Plasma samples from each animal were subjected to two-dimensional non-denaturing gel electrophoresis followed by electrotransfer to a nitrocellulose membrane and subsequent immunobloting for apoA-I, apoA-II, apoA-IV, and apoE. In wild-type mice, apoA-I was largely concentrated in α-mobility HDL particles (9.0-12.2 nm). Only trace amount of apoA-I was seen in the preβ-1 HDL subpopulation. The majority of apoE and all of apoA-IV were not associated with the apoA-I-containing HDL in these animals. ApoA-II was found to associate with the apoA-I-containing HDL, although only trace amounts were detected. In contrast, apoE-/- mice showed only trace amounts of apoA-I in the α-mobility region between 9.0-12.2 nm. Instead, the majority of the apoA-I of these animals had β/preβ-mobility. ApoE-/- mice also showed a greater number of apoA-I bands with sizes ranging from 7.0-13.0 nm. Notably, these bands were tightly packed, supporting that the apoA-I is in poorly-lipidated, discoidal forms. The size distribution of apoA-IV was similar to that seen in normal animals, however, both bands in the apoE-/- mice had slower mobility in the first dimension compared to the wild-type population. No apoE or apoA-II signals were detected in the apoE-/- mice.
Conclusion: Our results indicate that in mice, similar to situation observed in humans, the majority of apoA-I, apoE, and apoA-IV are in different HDL particles. In contrast to humans, in mice apoE appears to be necessary for the formation of normal (highly-lipidated and spherical) apoA-I-containing HDL particles. Therefore, results derived from apoE-/- mice cannot be extrapolated to human situations without taking these significant differences into consideration.
- © 2011 by American Heart Association, Inc.