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


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.
Baroukh
Nadine
N
Department of Genome Sciences, Lawrence Berkeley National Laboratory, Berkeley, Calif 94720, USA.
Bauge
Eric
E
Akiyama
Jennifer
J
Chang
Jessie
J
Afzal
Veena
V
Fruchart
Jean-Charles
JC
Rubin
Edward M
EM
Fruchart-Najib
Jamila
J
Pennacchio
Len A
LA
D000818:Animals; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000097:blood* / Q000235:genetics / Q000502:physiology; D001054:Apolipoproteins A; D001056:Apolipoproteins C / Q000097:blood* / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000097:blood / Q000502:physiology; D014280:Triglycerides / Q000097:blood*
C437704:APOA5 protein, human; C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D011993:Recombinant Fusion Proteins; D014280:Triglycerides