Overexpression of human ABCG1 does not affect atherosclerosis in fat-fed ApoE-deficient mice.
OBJECTIVE
The purpose of this study was to evaluate the effects of whole body overexpression of human ABCG1 on atherosclerosis in apoE(-/-) mice.


RESULTS
We generated BAC transgenic mice in which human ABCG1 is expressed from endogenous regulatory signals, leading to a 3- to 7-fold increase in ABCG1 protein across various tissues. Although the ABCG1 BAC transgene rescued lung lipid accumulation in ABCG1(-/-) mice, it did not affect plasma lipid levels, macrophage cholesterol efflux to HDL, atherosclerotic lesion area in apoE(-/-) mice, or levels of tissue cholesterol, cholesterol ester, phospholipids, or triglycerides. Subtle changes in sterol biosynthetic intermediate levels were observed in liver, with chow-fed ABCG1 BAC Tg mice showing a nonsignificant trend toward decreased levels of lathosterol, lanosterol, and desmosterol, and fat-fed mice exhibiting significantly elevated levels of each intermediate. These changes were insufficient to alter ABCA1 expression in liver.


CONCLUSIONS
Transgenic human ABCG1 does not influence atherosclerosis in apoE(-/-) mice but may participate in the regulation of tissue cholesterol biosynthesis.
Burgess
Braydon
B
Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
Naus
Kathryn
K
Chan
Jeniffer
J
Hirsch-Reinshagen
Veronica
V
Tansley
Gavin
G
Matzke
Lisa
L
Chan
Benny
B
Wilkinson
Anna
A
Fan
Jianjia
J
Donkin
James
J
Balik
Danielle
D
Tanaka
Tracie
T
Ou
George
G
Dyer
Roger
R
Innis
Sheila
S
McManus
Bruce
B
Lütjohann
Dieter
D
Wellington
Cheryl
C
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D003897:Desmosterol / Q000378:metabolism; D004041:Dietary Fats; D004195:Disease Models, Animal; D006706:Homeostasis; D006801:Humans; D008074:Lipoproteins / Q000172:deficiency / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015854:Up-Regulation
C419353:ABCG1 protein, human; C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; D004041:Dietary Fats; D008074:Lipoproteins; D003897:Desmosterol; D002784:Cholesterol