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

MacRae F. Linton, Robert V. Farese, Giulia Chiesa, David S. Grass, Peter Chin, Robert E Hammer, Helen H Hobbs, Stephen G. Young

Research output: Contribution to journalArticle

203 Scopus citations

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, β-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 (∼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.

Original languageEnglish (US)
Pages (from-to)3029-3037
Number of pages9
JournalJournal of Clinical Investigation
Volume92
Issue number6
DOIs
StatePublished - Dec 1993

Keywords

  • Cholesterol
  • Low density lipoproteins
  • P1 bacteriophage

ASJC Scopus subject areas

  • Medicine(all)

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