Effect of CETP on the plasma lipoprotein profile in four strains of transgenic mouse

The plasma cholesteryl ester transfer protein (CETP) plays a central role i n high-density lipoprotein (HDL) metabolism and reverse cholesterol transpo rt. There are conflicting views regarding whether or not excessive CETP act ivity is one of the risk factors of atherosclerosis. To study how much effe ct CETP can have on the profiles of plasma lipoproteins in vivo we produced four strains of transgenic mouse that expressed different levels of human CETP gene. We analyzed seven groups of mice that had different levels of CE TP expression. The cholesterol level of HDL, chylomicron (CM) and VLDL, int ermediate density lipoprotein (IDL) and LDL were proportionally changed in association with plasma CETP concentrations (2.9 +/- 0.6 to 37.4 +/- 1.7 mu g/ml) in an allelic dose-dependent manner. We further characterized one of the transgenic strains, CETP-4, by optimizing the experimental condition fo r the mouse model of atherosclerosis, and found that it would be useful for the development of therapeutics against atherosclerosis, (C) 2001 Academic Press.