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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1984.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Identification of Differentially Regulated Genes in Mildly Hyperlipidemic ApoE3-Leiden Mice by Use of Serial Analysis of Gene Expression

Arja J. Kreeft; Corina J.A. Moen; Marten H. Hofker; Rune R. Frants; Erno Vreugdenhil; Marion J.J. Gijbels; Louis M. Havekes; Nicole A. Datson

From the Department of Human and Clinical Genetics (A.J.K., C.J.A.M., R.R.F.), Leiden University Medical Centre, the Department of Medical Pharmacology (E.V., N.A.D.), University of Leiden, and TNO Health and Prevention Leiden (L.M.H.), Leiden, the Netherlands, and Cardiovascular Research Institute Maastricht (M.H.H., M.J.J.G.), University Maastricht, Maastricht, the Netherlands.

Correspondence to Dr Arja J. Kreeft, Department of Human and Clinical Genetics, Leiden University Medical Centre, Wassenaarseweg 72, 2333 AL Leiden, Netherlands. E-mail kreeft{at}lumc.nl

Although genes determining lipoprotein homeostasis and atherosclerosis are the subject of intensive investigation, only a subset of these genes is known at present. Hence, we do not have sufficient knowledge to explain the genetic basis of hyperlipidemia in the majority of subjects. Our aim was to identify novel genes and pathways underlying lipoprotein homeostasis by using serial analysis of gene expression. The liver expression profile of mild hyperlipidemic apolipoprotein E3-Leiden (E3L) transgenic mice was compared with that of the wild-type C57BL/6JIco (B6) mice. Over 18 000 liver transcripts of B6 as well as E3L mice were analyzed, representing >9400 unique genes. One hundred seventy-five genes showed altered expression between the strains (P<0.05). Although several of these genes belonged to known metabolic pathways, such as lipoprotein metabolism, detoxification processes, glycolysis, and the acute-phase response, most were novel. Differential gene expression of 8 of 10 genes tested could be confirmed by Northern blot analysis. This inventory of differentially expressed genes will provide a unique basis for detailed studies to gain more insight into their role in lipoprotein homeostasis and atherosclerosis.

Key Words: serial analysis of gene expression • gene expression profiles • hyperlipidemia • atherosclerosis

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