Locating a low density lipoprotein-targeting domain of human apolipoprotein B-100 by expressing a minigene construct in transgenic mice.
Through its interaction with the low density lipoprotein (LDL) receptor, apolipoprotein (apo) B-100 is a major determinant of LDL metabolism and plasma cholesterol. Its receptor binding ability is conformation-dependent and requires its expression on the right lipoprotein particles. The structural signal that targets apoB-100 to LDL is unknown. We have microinjected a human apoB-100 minigene construct comprising less than 25% of the apoB-100 sequence driven by the natural apoB promoter to produce transgenic mice. The transgene product was expressed at a high level and was present exclusively in the LDL of these animals. Analysis of the responsible sequence (residues 2878-3925 of apoB-100) reveals unique structural features that may be important in its role as an LDL-targeting domain.
Department of Cell Biology, Baylor College of Medicine, Houston, Texas.
W J
WJ
Xiong
E
E
Zsigmond
A M
AM
Gotto
K Y
KY
Lei
L
L
Chan
D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D004252:DNA Mutational Analysis; D015870:Gene Expression; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D009841:Oligonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins