Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice |
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Authors: | S L Hofmann D W Russell M S Brown J L Goldstein R E Hammer |
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Institution: | Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235. |
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Abstract: | 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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