Influence of mouse apolipoprotein A-II on plasma lipoproteins in transgenic mice.
The role of apolipoprotein A-II (apoA-II) in the metabolism of high density lipoproteins (HDL) is poorly understood. Previous studies of naturally occurring variations of apoA-II in mice have, however, suggested that apoA-II expression influences HDL size and concentration. We now provide definitive evidence of this using transgenic mice overexpressing mouse apoA-II. Thus, as compared with nontransgenic littermates, transgenic mice possessing 4-fold elevations of apoA-II mRNA and 2-3-fold elevations in plasma apoA-II levels exhibited more than a 2-fold increase in HDL levels as well as about a 25% increase in average HDL diameter. Overexpression of mouse apoA-II also resulted in a substantial decrease in the levels of apolipoprotein E associated with HDL, suggesting that apoA-II can displace apoE from HDL. The apoA-II transgenic mice also exhibited a 2-4-fold increase in plasma very low density and low density lipoprotein-cholesterol levels, suggesting novel interactions among the classes of plasma lipoproteins.
Department of Medicine, University of California, Los Angeles 90024.
C C
CC
Hedrick
L W
LW
Castellani
C H
CH
Warden
D L
DL
Puppione
A J
AJ
Lusis
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016632:Apolipoprotein A-I / Q000096:biosynthesis; D016633:Apolipoprotein A-II / Q000235:genetics* / Q000378:metabolism*; D001053:Apolipoproteins / Q000096:biosynthesis / Q000097:blood* / Q000302:isolation & purification; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D015183:Restriction Mapping; D012737:Sex Factors
D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001053:Apolipoproteins; D008074:Lipoproteins; D012333:RNA, Messenger