title: Analysis of apolipoprotein A5, c3, and plasma triglyceride concentrations in genetically engineered mice.
abstract: 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.
authors.affiliation: Department of Genome Sciences, Lawrence Berkeley National Laboratory, Berkeley, Calif 94720, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: Baroukh
authors.forename: Eric
authors.initials: E
authors.lastname: Bauge
authors.forename: Jennifer
authors.initials: J
authors.lastname: Akiyama
authors.forename: Jessie
authors.initials: J
authors.lastname: Chang
authors.forename: Veena
authors.initials: V
authors.lastname: Afzal
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Fruchart
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.forename: Jamila
authors.initials: J
authors.lastname: Fruchart-Najib
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
mesh_terms: 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*
chemical_list: 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