Expression of human apolipoprotein B and assembly of lipoprotein(a) in transgenic mice

Journal Article · Tue Mar 15 04:00:00 EST 1994 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.91.6.2130· OSTI ID:86515

Callow, M J; Stoltzfus, L J; Rubin, E M ^[1]; Lawn, R M ^[2]

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1. Lawrence Berkeley Lab., CA (United States)
2. Stanford Univ., CA (United States)

The atherogenic macromolecule lipoprotein(a) [Lp(a)] has resisted in vivo analyses partly because it is found in a limited number of experimental animals. Although transgenic mice expressing human apolipoprotein (a) [apo(a)] have previously been described, they failed to assemble Lp(a) particles because of the inability of human apo(a) to associate with mouse apolipoprotein B (apoB). The authors isolated a 90-kilobase P1 phagemid containing the human apoB gene and with this DNA generated 13 lines of transgenic mice of which 11 expressed human apoB. The human apoB transcript was expressed and edited in the liver of the transgenic mice. Plasma concentrations of human apoB, as well as low density lipoprotein (LDL), were related to transgene copy number; the transgenic line with the most copies of human apoB had a >4-fold increase in LDL cholesterol compared with nontransgenics and a lipoprotein profile similar to that of humans. When human apoB and apo(a) transgenic mice were bred together, plasma apo(a) in mice expressing both human proteins was tightly associated with lipoproteins in the LDL density region. These studies demonstrate the successful expression of human apoB and the efficient assembly of Lp(a) in mice.

• Sponsoring Organization: USDOE
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 86515
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 6 Vol. 91; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
APOLIPOPROTEINS
BIOSYNTHESIS
GENE REGULATION
LIPOPROTEINS
TRANSGENIC MICE