title: Overexpression of human ABCG1 does not affect atherosclerosis in fat-fed ApoE-deficient mice.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
authors.forename: Braydon
authors.initials: B
authors.lastname: Burgess
authors.forename: Kathryn
authors.initials: K
authors.lastname: Naus
authors.forename: Jeniffer
authors.initials: J
authors.lastname: Chan
authors.forename: Veronica
authors.initials: V
authors.lastname: Hirsch-Reinshagen
authors.forename: Gavin
authors.initials: G
authors.lastname: Tansley
authors.forename: Lisa
authors.initials: L
authors.lastname: Matzke
authors.forename: Benny
authors.initials: B
authors.lastname: Chan
authors.forename: Anna
authors.initials: A
authors.lastname: Wilkinson
authors.forename: Jianjia
authors.initials: J
authors.lastname: Fan
authors.forename: James
authors.initials: J
authors.lastname: Donkin
authors.forename: Danielle
authors.initials: D
authors.lastname: Balik
authors.forename: Tracie
authors.initials: T
authors.lastname: Tanaka
authors.forename: George
authors.initials: G
authors.lastname: Ou
authors.forename: Roger
authors.initials: R
authors.lastname: Dyer
authors.forename: Sheila
authors.initials: S
authors.lastname: Innis
authors.forename: Bruce
authors.initials: B
authors.lastname: McManus
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Cheryl
authors.initials: C
authors.lastname: Wellington
mesh_terms: 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
chemical_list: 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