Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice.
A complementary DNA encoding the human low density lipoprotein (LDL) receptor under control of the mouse metallothionein-I promoter was injected into fertilized mouse eggs, and a strain of mice expressing high levels of LDL receptors was established. After administration of cadmium, these mice cleared intravenously injected 125I-labeled LDL from blood eight to ten times more rapidly than did normal mice. The plasma concentrations of apoproteins B-100 and E, the two ligands for the LDL receptor, declined by more than 90 percent after cadmium treatment, but the concentration of another apoprotein, A-I, was unaffected. Therefore, overexpression of an endocytotic receptor can dramatically lower the ambient concentration of its ligand in vivo.
Hofmann
S L
SL
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Russell
D W
DW
Brown
M S
MS
Goldstein
J L
JL
Hammer
R E
RE
D000818:Animals; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005260:Female; D005796:Genes; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood*; D051379:Mice; D008822:Mice, Transgenic; D010957:Plasmids; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D014158:Transcription, Genetic
D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D004247:DNA