ABCA1 mRNA and protein distribution patterns predict multiple different roles and levels of regulation.
Mutations in ABCA1 cause the allelic disorders familial hypolipoproteinemia and Tangier Disease. To identify where ABCA1 was likely to have a functional role, we determined the cellular and tissue-specific patterns of murine ABCA1 expression. RT-PCR and Western blot analysis on dissected murine tissues demonstrated broad expression of ABCA1 mRNA and protein in many tissues with prominent protein expression in liver, testis, and adrenal tissue. In situ hybridization and immunohistochemistry experiments demonstrated specific patterns of ABCA1 expression at the cellular level, with hepatocytes, the epithelial lining of the digestive system and bladder, the proximal convoluted tubule of the kidney, and Purkinje and cortical pyramidal neurons containing abundant ABCA1 protein. Significant discordance between relative mRNA and protein expression patterns suggests the possibility of post-transcriptional regulation of ABCA1 expression in selected cells or tissues. We also show that ABCA1 protein levels are up-regulated specifically in the liver after exposure to an atherogenic diet for 7 days, supporting a major role for the liver in dietary modulation of HDL-C levels. Our observations show that ABCA1 is expressed in a pattern consistent with its role in HDL-C metabolism. Additionally, ABCA1 may have important functional roles in other cell types independent of HDL-C regulation.
Wellington
Cheryl L
CL
Centre for Molecular Medicine and Therapeutics, St. Paul's Hospital/Providence Health Care-University of British Columbia, Canada.
Walker
Elizabeth K Y
EK
Suarez
Agripina
A
Kwok
Anita
A
Bissada
Nagat
N
Singaraja
Roshni
R
Yang
Yu-Zhou
YZ
Zhang
Lin-Hua
LH
James
Erick
E
Wilson
Janet E
JE
Francone
Omar
O
McManus
Bruce M
BM
Hayden
Michael R
MR
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002791:Cholesterol, Dietary / Q000009:adverse effects; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D002791:Cholesterol, Dietary; D012333:RNA, Messenger