International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Arja Kreeft
Department of Human Genetics
Leiden University Medical Centre
Wassenaarseweg 72
Leiden 2333 AL
The Netherlands

Co-Authors: 1) Moen CJA, 2) Hofker MH, 1) Frants RR, 2) Gijbels MJJ, 1) Vreugdenhil E, 3) Havekes LM, 4) Porter G, 1) Datson NA
Institutions: 1)Leiden University Medical Centre 2)CARIM, University Maastricht 3)TNO-PG  Leiden, 4)Incyte Genomics

To identify new genes that are involved in the development of hyperlipidemia and atherosclerosis, transgenic APOE3Leiden (E3L) mice are used. These mice carry the human APOE3Leiden and APOC1 genes on a C57BL/6J (B6) background. They have high lipid levels due to a defect in the uptake of remnant lipoproteins from the plasma. Additionally, they show a profound diet-induced hyperlipidemia and are susceptible to cafestol, a cholesterol-raising factor from coffee. Firstly, the effect of the transgenes on gene expression has been studied. Liver expression profiles have been obtained from B6 and E3L mice on chow diet, using Serial Analysis of Gene Expression (SAGE). Over 18,000 tags were analyzed from each strain. The total of 37,000 tags revealed 9400 unique genes. Of these 9400 different genes, 175 genes were differentially expressed (p < 0.05). Twenty-nine percent of the differentially expressed genes were known genes, 15% ESTs and 56% is unknown. Liver RNAs used for SAGE (E3L versus B6) were also hybridized to Affymetrix Genechips (Mu11KB). Secondly, to identify dietary response genes, lipid levels of B6 and E3L mice on different diets were measured and gene expression profiles were studied using cDNA microarrays (Incyte) containing 9500 genes. Some 266 genes were found to be differentially expressed for at least two fold in one or more conditions. Currently, these expression data are being evaluated in more detail.

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