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Journal of Lipid Research, Vol. 46, 2061-2071, October 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Alternate transcripts expressed in response to diet reflect tissue-specific regulation of ABCA1

Roshni R. Singaraja^*, Erick R. James^*, Jennifer Crim, Henk Visscher^*, Alu Chatterjee and Michael R. Hayden^1,*

^* Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
Pfizer Global Research and Development, Ann Arbor, MI 48105

Published, JLR Papers in Press, July 16, 2005. DOI 10.1194/jlr.M500133-JLR200

¹ To whom correspondence should be addressed. e-mail: mrh{at}cmmt.ubc.ca

ABCA1 is essential for the transport of lipids across plasma membranes and for the maintenance of plasma HDL-cholesterol levels. The transcriptional regulation of ABCA1 is complex and is currently poorly understood. We previously generated human ABCA1 bacterial artificial chromosome transgenic mice that expressed RNA and protein, which allowed us to identify three alternate ABCA1 transcripts. Each transcript arises from different exon 1 sequences (exon1b, exon1c, and exon1d) that are spliced directly into exon 2, which contains the ATG site, and all generate full-length protein. We have now determined the tissue-specific expression of each of these transcripts in humans and mice and have shown that their patterns of expression are similar. Exon1d transcript is predominantly expressed in liver and macrophages and is preferentially increased in the liver in response to a high-fat diet. The exon1b transcript is expressed predominantly in liver, testis, and macrophages, but it is only upregulated in macrophages in response to a high-fat diet. The exon1c transcript is ubiquitously expressed and is upregulated in the brain, stomach, and other tissues in mice on a high-fat diet.

Our data indicate that specific transcripts in different tissues play key roles in alterations of ABCA1-mediated changes in HDL levels and atherosclerosis in response to environmental stimuli.

Supplementary key words mouse model • liver • macrophage • high density lipoprotein • atherosclerosis • high-fat diet • lipid efflux • ATP binding cassette transporter A1

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