Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).

Linton MF, Farese RV, Chiesa G, Grass DS, Chin P, Hammer RE, Hobbs HH, Young SG
J Clin Invest. 1993 92 (6): 3029-37

PMID: 8254057 · PMCID: PMC288508 · DOI:10.1172/JCI116927

The B apolipoproteins, apo-B48 and apo-B100, are key structural proteins in those classes of lipoproteins considered to be atherogenic [e.g., chylomicron remnants, beta-VLDL, LDL, oxidized LDL, and Lp(a)]. Here we describe the development of transgenic mice expressing high levels of human apo-B48 and apo-B100. A 79.5-kb human genomic DNA fragment containing the entire human apo-B gene was isolated from a P1 bacteriophage library and microinjected into fertilized mouse eggs. 16 transgenic founders expressing human apo-B were generated, and the animals with the highest expression had plasma apo-B100 levels nearly as high as those of normolipidemic humans (approximately 50 mg/dl). The human apo-B100 in transgenic mouse plasma was present largely in lipoproteins of the LDL class as shown by agarose gel electrophoresis, chromatography on a Superose 6 column, and density gradient ultracentrifugation. When the human apo-B transgenic founders were crossed with transgenic mice expressing human apo(a), the offspring that expressed both transgenes had high plasma levels of human Lp(a). Both the human apo-B and Lp(a) transgenic mice will be valuable resources for studying apo-B metabolism and the role of apo-B and Lp(a) in atherosclerosis.

MeSH Terms (21)

Animals Apolipoprotein B-100 Apolipoproteins B Base Sequence Blotting, Southern DNA DNA Primers Electrophoresis, Agar Gel Female Humans Immunoblotting Lipoprotein(a) Lipoproteins Male Mice Mice, Transgenic Microinjections Molecular Sequence Data Polymerase Chain Reaction Restriction Mapping Transcription, Genetic

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