Main content area

Phenotypic analysis of mice expressing exclusively apolipoprotein B48 or apolipoprotein B100

Farese, R.V. Jr., Veniant, M.M., Cham, C.M., Flynn, L.M., Pierotti, V., Loring, J.F., Traber, M., Ruland, S., Stokowski, R.S., Huszar, D.
Proceedings of the National Academy of Sciences of the United States of America 1996 v.93 no.13 pp. 6393-6398
blood lipids, phenotype, structural genes, blood proteins, apolipoproteins, very low density lipoprotein, triacylglycerols, mice, homologous recombination, low density lipoprotein, cholesterol, mutants, gene targeting, blood plasma, site-directed mutagenesis, embryogenesis
Apolipoprotein (apo)-B is found in two forms in mammals: apo-B100, which is made in the liver and the yolk sac, and apo-B48, a truncated protein made in the intestine. To provide models for understanding the physiologic purpose for the two forms of apo-B, we used targeted mutagenesis of the apo-B gene to generate mice that synthesize exclusively apo-B48 (apo-B48-only mice) and mice that synthesize exclusively apo-B100 (apo-B100-only mice). Both the apo-B48-only mice and apo-B100-only mice developed normally, were healthy, and were fertile. Thus, apo-B48 synthesis was sufficient for normal embryonic development, and the synthesis of apo-B100 in the intestines of adult mice caused no readily apparent adverse effects on intestinal function or nutrition. Compared with wild-type mice fed a chow diet, the levels of low density lipoprotein (LDL)-cholesterol and very low density lipoprotein- and LDL-triacylglycerols were lower in apo-B48-only mice and higher in the apo-B100-only mice. In the setting of apo-E-deficiency, the apo-B100-only mutation lowered cholesterol levels, consistent with the fact that apo-B100-lipoproteins can be cleared from the plasma via the LDL receptor, whereas apo-B48-lipoproteins lacking apo-E cannot. The apo-B48-only and apo-B100-only mice should prove to be valuable models for experiments designed to understand the purpose for the two forms of apo-B in mammalian metabolism.