Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).
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.
Linton
M F
MF
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100.
Farese
R V
RV
Chiesa
G
G
Grass
D S
DS
Chin
P
P
Hammer
R E
RE
Hobbs
H H
HH
Young
S G
SG
D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000008:administration & dosage / Q000032:analysis; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D015151:Immunoblotting; D017270:Lipoprotein(a) / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008074:Lipoproteins / Q000097:blood / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D014158:Transcription, Genetic
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D017931:DNA Primers; D017270:Lipoprotein(a); D008074:Lipoproteins; D004247:DNA