Transgenic mice expressing both human apolipoprotein B and human CETP have a lipoprotein cholesterol distribution similar to that of normolipidemic humans

Transgenic mice expressing both human apolipoprotein (apo) B and human cholesteryl ester transfer protein (CETP) have been developed. When fed a normal mouse chow diet, the apoB/CETP double transgenic animals had threefold higher serum CETP activity than humans and had human apoB levels that were similar to those of normolipidemic humans. When compared with nontransgenic mice, the total serum cholesterol levels in the female apoB/CETP transgenic animals were increased significantly. Serum HDL cholesterol levels were decreased significantly in both male and female apoB/CETP transgenic animals. The percentages of the total cholesterol within the HDL, LDL, and VLDL fractions of the apoB/CETP animals were approximately 30%, 65%, and 5%, respectively, similar to the distribution of cholesterol in the plasma of normolipidemic humans. Thus, by expressing both human apoB and human CETP, the lipoprotein cholesterol distribution in the serum of a chow-fed mouse was transformed into one that resembles a human profile.