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Publication : Analysis of apolipoprotein A5, c3, and plasma triglyceride concentrations in genetically engineered mice.

First Author  Baroukh N Year  2004
Journal  Arterioscler Thromb Vasc Biol Volume  24
Issue  7 Pages  1297-302
PubMed ID  15117734 Mgi Jnum  J:102319
Mgi Id  MGI:3607361 Doi  10.1161/01.ATV.0000130463.68272.1d
Citation  Baroukh N, et al. (2004) Analysis of apolipoprotein A5, c3, and plasma triglyceride concentrations in genetically engineered mice. Arterioscler Thromb Vasc Biol 24(7):1297-302
abstractText  OBJECTIVE: Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are strongly altered by changes in the expression of either of these 2 genes. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. These similar findings raised the issue of the relationship between these 2 genes and altered triglycerides. METHODS AND RESULTS: To address this issue, we generated independent lines of mice that either overexpressed ('double transgenic') or completely lacked ('double knockout') both apolipoprotein genes. We report that both 'double transgenic' and 'double knockout' mice display normal triglyceride concentrations compared with overexpression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the 'double transgenic' mice are approximately 500-fold lower than human ApoCIII levels, supporting ApoAV as a potent triglyceride modulator despite its low concentration. CONCLUSIONS: Together, these data support that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.
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