Principal Investigators: |
|
| Prof. Dr. med. Daniel Teupser | Prof. Dr. med. Joachim Thiery |
| Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics | Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics |
| Universität Leipzig | Universität Leipzig |
| Paul-List-Straße 13-15 | Paul-List-Straße 13-15 |
| 04103 Leipzig | 04103 Leipzig |
| Phone: +49 341 97 22204 | Phone: +49 341 97 22200 |
| Fax: +49 341 97 22209 | Fax: +49 341 97 22209 |
| teupser@medizin.uni-leipzig.de | thiery@medizin.uni-leipzig.de |
Summary of the Subproject:
Obesity is considered as a risk factor of atherosclerosis. Genetic factors play an important role in weight regulation as well as in the development of atherosclerosis. In our preliminary work we have generated 384 F2 animals from an intercross of atherosclerosis susceptible C57BL/6 and atherosclerosis resistant BALB/cByJ mice on the LDL-receptor-deficient background. Quantitative trait locus (QTL) mapping led to the identification of a novel locus of atherosclerosis susceptibility on chromosome 2 (Chr2). Interestingly, the locus co-segregated with a locus for the mass of the omental, parametral/epididymal and perirenal fat, and the total fat mass. The underlying hypothesis of the current project is that atherosclerosis and mass of fatty tissue are regulated by identical genes at the Chr2 locus. To identify the potential candidate genes in the region, we determine mRNA expression in tissue of a subgroup of 176 mice using genome-wide expression arrays and perform expression QTL (eQTL) mapping using the existing genetic markers of these animals. Genes at the Chr2 locus, which show significant eQTLs, will be analysed in functional studies in cultivated cells and tissues of parental strains in more detail. To examine the influence on atherosclerosis and mass of fatty tissue in-vivo, candidate genes will be analyzed using transgenic animal models.
Publications:
- Burkhardt R, Sündermann S, Ludwig D, Ceglarek U, Holdt LM, Thiery J, Teupser D. Co-segregation of aortic root atherosclerosis and intermediate lipid phenotypes on chromosomes 2 and 8 in an intercross of C57BL/6 and BALBc/ByJ LDLR-/- mice. Arterioscler Thromb Vasc Biol. 2011; Epub ahead of print.