on April 29, 2004
Published online before print April 29, 2004, doi: 10.1161/01.ATV.0000130463.68272.1d
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Submitted on March 11, 2004
Accepted on April 19, 2004
Analysis of Apolipoprotein A5, C3, and Plasma Triglyceride Concentrations in Genetically Engineered Mice
Nadine Baroukh ;
From Genome Sciences Department (N.B., J.A., J.C., V.A., E.M.R., L.A.P.), Lawrence Berkeley National Laboratory, Berkeley, Calif; Department of Atherosclerosis (E.B., J.-C.F., J.F.), Pasteur Institute, Lille, France; United States Department of Energy Joint Genome Institute (E.M.R., L.A.P.), Walnut Creek, Calif.
* To whom correspondence should be addressed. E-mail: LAPennacchio{at}lbl.gov.
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 
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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