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

199 Citations (Scopus)

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
StatePublished - Dec 1993

Fingerprint

Lipoprotein(a)
Apolipoproteins
Transgenic Mice
Apolipoproteins B
Bacteriophage P1
Chylomicron Remnants
Apolipoprotein B-48
Agar Gel Electrophoresis
Zygote
Ultracentrifugation
Transgenes
LDL Lipoproteins
Lipoproteins
Gel Chromatography
Atherosclerosis

Keywords

  • Cholesterol
  • Low density lipoproteins
  • P1 bacteriophage

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Linton, M. F., Farese, R. V., Chiesa, G., Grass, D. S., Chin, P., Hammer, R. E., ... Young, S. G. (1993). Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein (a). Journal of Clinical Investigation, 92(6), 3029-3037.

Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein (a). / Linton, MacRae F.; Farese, Robert V.; Chiesa, Giulia; Grass, David S.; Chin, Peter; Hammer, Robert E; Hobbs, Helen H; Young, Stephen G.

In: Journal of Clinical Investigation, Vol. 92, No. 6, 12.1993, p. 3029-3037.

Research output: Contribution to journalArticle

Linton, MF, Farese, RV, Chiesa, G, Grass, DS, Chin, P, Hammer, RE, Hobbs, HH & Young, SG 1993, 'Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein (a)', Journal of Clinical Investigation, vol. 92, no. 6, pp. 3029-3037.
Linton, MacRae F. ; Farese, Robert V. ; Chiesa, Giulia ; Grass, David S. ; Chin, Peter ; Hammer, Robert E ; Hobbs, Helen H ; Young, Stephen G. / Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein (a). In: Journal of Clinical Investigation. 1993 ; Vol. 92, No. 6. pp. 3029-3037.
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AU - Chin, Peter

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