Transgenic rabbits expressing human lipoprotein lipase

To study the functions of lipoprotein lipase (LPL) in lipid and lipoprotein metabolism and the relationship between LPL and atherosclerosis, we genera ted transgenic rabbits expressing the human LPL gene. A total of 4045 Japan ese white rabbit embryos were microinjected with a 3.8-kb SalI/HindIII frag ment containing the chicken beta-actin promoter, human LPL cDNA and rabbit beta-globin with poly (A) signals, and then transplanted into 116 recipient rabbits. Of the 166 pups born, six pups were transgenic as confirmed by So uthern blot analysis. A Northern blot analysis revealed that human LPL was expressed by a number of tissues including the heart, kidney, adrenal gland and intestine. One transgenic rabbit showed up to 3-fold increased LPL act ivity in post-heparin plasma compared to that in nontransgenic rabbits. Hum an LPL expression in various tissues of transgenic rabbits was further eluc idated by in situ hybridization and immunostaining. Since rabbits are super ior to mice as a model of atherosclerosis, this transgenic rabbit model sho uld provide a valuable tool for the study of LPL in lipid metabolism and at herosclerosis.