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Science 11 March 1988:
Vol. 239. no. 4845, pp. 1277 - 1281
DOI: 10.1126/science.3344433
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Articles

Science, Vol 239, Issue 4845, 1277-1281
Copyright © 1988 by American Association for the Advancement of Science

articles

Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice

SL Hofmann, DW Russell, MS Brown, JL Goldstein, and RE Hammer

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.

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.


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