Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).
Open Access
- 1 December 1993
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 92 (6), 3029-3037
- https://doi.org/10.1172/jci116927
Abstract
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.Keywords
This publication has 51 references indexed in Scilit:
- Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery.JCI Insight, 1993
- Cloning high molecular weight DNA fragments by the bacteriophage P1 systemTrends in Genetics, 1992
- Arterial hardening in miceNature, 1992
- Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein EScience, 1992
- Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cellsCell, 1992
- Modification of the apolipoprotein B gene in HepG2 cells by gene targeting.JCI Insight, 1992
- Ability of the LDL receptor from several animal species to recognize the human apo B binding domain: studies with LDL from familial defective apo B-100Atherosclerosis, 1992
- Lipoprotein (a). Heterogeneity and biological relevance.JCI Insight, 1990
- Determination of cysteine on low-density lipoproteins using the fluorescent probe, 5-iodoacetamidofluoresceineBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1990
- Characterization of an abnormal species of apolipoprotein B, apolipoprotein B-37, associated with familial hypobetalipoproteinemia.JCI Insight, 1987