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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.