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

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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.

Original languageEnglish (US)
Pages (from-to)1277-1281
Number of pages5
JournalScience
Volume239
Issue number4846
StatePublished - 1988

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LDL Receptors
LDL Lipoproteins
Transgenic Mice
Cadmium
Ligands
Apoproteins
Metallothionein
Zygote
Apolipoproteins B
Apolipoproteins E
Complementary DNA

ASJC Scopus subject areas

  • General

Cite this

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title = "Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice",
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.",
author = "Hofmann, {Sandra L} and Russell, {David W} and Brown, {Michael S} and Goldstein, {Joseph L} and Hammer, {Robert E}",
year = "1988",
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T1 - Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice

AU - Hofmann, Sandra L

AU - Russell, David W

AU - Brown, Michael S

AU - Goldstein, Joseph L

AU - Hammer, Robert E

PY - 1988

Y1 - 1988

N2 - 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.

AB - 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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