Genetic determinants controlling lipid deposits in different wild type strains of zebrafish (Danio rerio)

Objectives: Zebrafish (Danio rerio) has been established as a brilliant model to study dyslipidemia or atherosclerosis due to the remarkable similarities with humans in lipid and lipoprotein metabolism. In contrast to mice, zebrafish show lipoprotein oxidation and dyslipidemia after feeding with a high cholesterol diet for as short as 15 day's time period, even without any genetic intervention. Methods: Here, five different wild type strains of zebrafish i.e. AB, TU, TL, WIK and LEO were tested. Interestingly, after feeding a high cholesterol diet (4% cholesterol extra) we observed a strong variability in lipid accumulation among the tested strains. Results: Our results demonstrated AB strain to be most susceptible and TU strain to be more resistant, whereas TL, WIK and LEO strains demonstrated a moderate phenotype for lipid deposits. Conclusions: We claim to identify genetic loci controlling this variability using the classical QTL-analysis. Therefore, breeding of F2 generation zebrafish from the most susceptible and resistant strain i.e. AB and TU respectively is in progress. In addition, we will put new insights into the possible pathways leading to the observed lipid deposits variation between AB and TU strains on gene expression level by conducting gene expression profiling. Identification of genetic loci by QTL-analysis for controlling lipid accumulation and leading to an almost resistant phenotype for lipid accumulation in zebrafish might have important implications for humans as well. Lipid accumulation is considered as an early step initiating atherosclerosis. Thus our results will contribute considerably to advance the identification of novel targets for dyslipidaemia and therapeutic objectives for atherosclerosis.