Application of gene targeting to the study of atherosclerosis

点击翻译按钮获取中文摘要

In order to elucidate the role of multiple genetic factors on the process of atherosclerosis, we used the mouse developmental biological technics, especially gene targeting using homologous recombination in ES cells. We established the endothelin-1 knockout mice, macrophage scavenger receptor knockout mouse, and other gene targeted mice strains in order to analyze the roles of these genes, and the mechanism how endothelial cells, smooth muscle cells and macrophages are involved in the atherogenesis. The heterozygout mice deficient in endothekin-1 indicated the increase of blood pressure. Macrophage obtained from the homozygout for scavenger receptor deficiency indicated the marked decrease in both acetyl-LDL degradation and oxidized LDL degradation. Adding to this, these macrophage also indicated the decrease in the binding activity of both AGE and LPS.The function of these genes in vivo is different from those studied in vitro, and mouse developmental biological technics, especially gene targeting provide a nice tool to analyze these problems.