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Differential expression and function of ABCG1 and ABCG4 during development and aging

Bojanic, Dragana D. and Tarr, Paul T. and Gale, Greg D. and Smith, Desmond J. and Bok, Dean and Chen, Bryan and Nusinowitz, Steven and Lövgren-Sandblom, Anita and Björkhem, Ingemar and Edwards, Peter A. (2010) Differential expression and function of ABCG1 and ABCG4 during development and aging. Journal of Lipid Research, 51 (1). pp. 169-181. ISSN 0022-2275. PMCID PMC2789777.

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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 β-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.

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Additional Information:© 2010 American Society for Biochemistry and Molecular Biology. Manuscript received 20 May 2009 and in revised form 9 July 2009. Originally published In Press as doi:10.1194/M900250-JLR200 on July 26, 2009. This work was supported by grants from the National Institutes of Health (NIH-30568 and NIH-68445 to P. A. E.), Grant RO1MH71779 (to D. J. S.) from the Laubisch Fund, an HDL Pfizer Award (to P. A. E.) and the Swedish Science Council and Brain Power (to I. B.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
Funding AgencyGrant Number
Laubisch FundRO1MH71779
Swedish Science Council and Brain PowerUNSPECIFIED
Subject Keywords:oxysterols; liver X receptor; sterol regulatory element binding protein-2; central nervous system
Issue or Number:1
PubMed Central ID:PMC2789777
Record Number:CaltechAUTHORS:20100202-112202927
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Official Citation:Dragana D. Bojanic, Paul T. Tarr, Greg D. Gale, Desmond J. Smith, Dean Bok, Bryan Chen, Steven Nusinowitz, Anita Lövgren-Sandblom, Ingemar Björkhem, and Peter A. Edwards Differential expression and function of ABCG1 and ABCG4 during development and aging J. Lipid Res. 51: 169-181. First published online as doi:10.1194/M900250-JLR200
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17376
Deposited By: Jason Perez
Deposited On:16 Feb 2010 23:44
Last Modified:03 Oct 2019 01:27

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