title: Differential expression and function of ABCG1 and ABCG4 during development and aging.
abstract: ABCG1 and ABCG4 are highly homologous members of the ATP binding cassette (ABC) transporter family that regulate cellular cholesterol homeostasis. In adult mice, ABCG1 is known to be expressed in numerous cell types and tissues, whereas ABCG4 expression is limited to the central nervous system (CNS). Here, we show significant differences in expression of these two transporters during development. Examination of beta-galactosidase-stained tissue sections from Abcg1(-/-)LacZ and Abcg4(-/-)LacZ knockin mice shows that ABCG4 is highly but transiently expressed both in hematopoietic cells and in enterocytes during development. In contrast, ABCG1 is expressed in macrophages and in endothelial cells of both embryonic and adult liver. We also show that ABCG1 and ABCG4 are both expressed as early as E12.5 in the embryonic eye and developing CNS. Loss of both ABCG1 and ABCG4 results in accumulation in the retina and/or brain of oxysterols, in altered expression of liver X receptor and sterol-regulatory element binding protein-2 target genes, and in a stress response gene. Finally, behavioral tests show that Abcg4(-/-) mice have a general deficit in associative fear memory. Together, these data indicate that loss of ABCG1 and/or ABCG4 from the CNS results in changes in metabolic pathways and in behavior.
authors.affiliation: Department of Biological Chemistry at UCLA Los Angeles, CA 90095, USA.
authors.forename: Dragana D
authors.initials: DD
authors.lastname: Bojanic
authors.forename: Paul T
authors.initials: PT
authors.lastname: Tarr
authors.forename: Greg D
authors.initials: GD
authors.lastname: Gale
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Smith
authors.forename: Dean
authors.initials: D
authors.lastname: Bok
authors.forename: Bryan
authors.initials: B
authors.lastname: Chen
authors.forename: Steven
authors.initials: S
authors.lastname: Nusinowitz
authors.forename: Anita
authors.initials: A
authors.lastname: Lövgren-Sandblom
authors.forename: Ingemar
authors.initials: I
authors.lastname: Björkhem
authors.forename: Peter A
authors.initials: PA
authors.lastname: Edwards
mesh_terms: D000070996:ATP Binding Cassette Transporter, Subfamily G; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D003214:Conditioning, Classical; D004622:Embryo, Mammalian / Q000378:metabolism*; D005239:Fear; D018507:Gene Expression Regulation, Developmental; D008074:Lipoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D012160:Retina / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: C487540:ABCG1 protein, mouse; D000070996:ATP Binding Cassette Transporter, Subfamily G; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; C486685:Abcg4 protein, mouse; D008074:Lipoproteins; D001616:beta-Galactosidase