Published online before print April 29, 2004, doi: 10.1161/01.ATV.0000130463.68272.1d
© 2004 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Analysis of Apolipoprotein A5, C3, and Plasma Triglyceride Concentrations in Genetically Engineered Mice
From the Genome Sciences Department (N.B., J.A., J.C., V.A., E.M.R., L.A.P.), Lawrence Berkeley National Laboratory, Berkeley, Calif; the Department of Atherosclerosis (E.B., J.-C.F., J.F.-N.), Pasteur Institute, Lille, France; United States Department of Energy Joint Genome Institute (E.M.R., L.A.P.), Walnut Creek, Calif.
Correspondence to Dr Len A. Pennacchio, Department of Genome Sciences, MS 84-171, One Cyclotron Road, Lawrence Berkeley National Laboratory, Berkeley, CA 94720. 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.
To address the relationship between the apolipoprotein A5 and C3 genes, we generated independent lines of mice that either overexpressed or completely lacked both genes. We report both lines display normal triglyceride concentrations compared with overexpression or deletion of either gene alone. Together, these data support that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.
Key Words: apolipoprotein • triglyceride • transgenic mice
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