Assembly of lipoprotein (a) in transgenic rabbits expressing human apolipoprotein (a)

The study of human lipoprotein (a) [Lp(a)] has been hampered due to the lac k of appropriate animal models since apolipoprotein (a) [apo(a)] is found o nly in primates and humans. In addition, human apo(a) in transgenic mice ca n not bind to murine apoB to form Lp(a) particles. In this study, we genera ted three independent transgenic rabbits expressing human apo(a) in their p lasma at 1.8-4.5 mg/dl. In the plasma of transgenic rabbits, unlike the pla sma of transgenic mice, about 80% of the apo(a) was covalently associated w ith rabbit apo-B and was contained in the fractions with density 1.02-1.10 g/ml, indicating the formation of Lp(a). These results suggest that transge nic rabbits expressing human apo(a) exhibit efficient assembly of Lp(a) and can be used as an animal model for the study of human Lp(a). (C) 1999 Acad emic Press.