J. Lipid Res.
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A more recent version of this article appeared on October 1, 2005

Papers In Press, published online ahead of print July 16, 2005
J. Lipid Res., doi:10.1194/jlr.M500133-JLR200
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Submitted on April 5, 2005
Revised on June 30, 2005
Accepted on July 5, 2005

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

Medical Genetics, University of British Columbia, Vancouver, BC V5Z 4H4

Corresponding Author: mrh{at}cmmt.ubc.ca

ABCA1 is essential for transport of lipids across plasma membranes and for the maintenance of plasma HDL-C levels. The transcriptional regulation of ABCA1 is complex and is currently poorly understood. We previously generated human ABCA1 BAC transgenic mice which expressed RNA and protein, and allowed us to identify three alternate ABCA1 transcripts. Each transcript arises from different exon1 sequences, exon1b, exon1c, and exon1d, that are directly spliced into exon2 which contains the ATG site and all generate full length protein. We have now determined tissue specific expression of each of these transcripts in humans and mice and shown that their pattern of expression is similar. Exon1d transcript is predominantly expressed in liver and macrophages, and is preferentially increased in the liver in response to high fat diet. The exon1b transcript is expressed predominantly in liver, testis and macrophages, but only up-regulated in macrophages in response to high fat diet. The exon1c transcript is ubiquitously expressed and is up-regulated 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.


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Y. J. Jiang, B. Lu, P. Kim, P. M. Elias, and K. R. Feingold
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