International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Dr. Corina Moen
Leiden University Medical Center
Dept. of Human Genetics
Wassenaarseweg 72
2333 AL Leiden
The Netherlands

Co-Authors: 2) Gijbels, M.J.J, 1) Kreeft, A.J, 2) van Gorp, P.J.J, 1) Bogaerts, M, 1) Tholens, A, 3) Havekes, L.M, 4) Porter, G, 1) Frants, R.R, 2) Hofker, M.H
Institutions: 1) Leiden University Medical Center, 2) CARIM, University Maastricht, 3) TNO-PG, Leiden, The Netherlands, 4) Incyte Genomics, Paolo Alto

The APOE3Leiden mutation is associated with Familial Dysbetalipoproteinemia characterized by hyperlipidemia and atherosclerosis. The clinical phenotype of carriers is highly variable, due to modifier genes and environmental factors. To identify these genes, we use the transgenic APOE3Leiden (E3L) mouse model. We follow 2 complementary approaches: 1) QTL mapping: FVB/N mice carry modifier genes that increase the levels of cholesterol as well as triglycerides of E3L on different diets and also influence susceptibility to atherosclerosis. To map these genes, we are performing a genome scan with 130 markers on 279 (E3L x FVB) F2 mice. The lipid levels of these F2 mice on 4 different diets have been measured as well as their susceptibility to atherosclerosis. 2) Micro arraying to identify genes that are differentially regulated under various genetic or dietary conditions: a) during overexpression of APOE, b) in E3L mice on different diets and c) in F2 mice carrying a particular QTL. Initially, livers of B6 and E3L mice fed different diets, were analyzed on Incyte Life Arrays carrying 9500 genes. Some 231 genes were found to be differentially expressed at least 2 fold. Firstly, we will investigate which of these genes coincide with already mapped QTLs from literature. Subsequently, we will integrate the expression data in our mapping study, facilitating the identification of novel (candidate) genes and pathways involved.

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