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.

[1]  M. Brown,et al.  Visualization of lipoprotein receptors by ligand blotting. , 1983, The Journal of biological chemistry.

[2]  D. Russell,et al.  Deletion of clustered O-linked carbohydrates does not impair function of low density lipoprotein receptor in transfected fibroblasts. , 1986, The Journal of biological chemistry.

[3]  M. Brown,et al.  Purification of the low density lipoprotein receptor, an acidic glycoprotein of 164,000 molecular weight. , 1982, The Journal of biological chemistry.

[4]  D. Steiner,et al.  Structure and evolution of the insulin gene. , 1985, Annual review of genetics.

[5]  R. Palmiter,et al.  Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring , 1982, Cell.

[6]  M. Brown,et al.  A receptor-mediated pathway for cholesterol homeostasis. , 1986, Science.

[7]  C. A. Thomas,et al.  Recovery of DNA segments from agarose gels. , 1980, Analytical biochemistry.

[8]  D. Melton,et al.  Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. , 1984, Nucleic acids research.

[9]  J. Weinstein,et al.  Acetoacetylated Lipoproteins Used to Distinguish Fibroblasts from Macrophages In Vitro by Fluorescence Microscopy , 1981, Arteriosclerosis.

[10]  M. Brown,et al.  Increased mRNA for low density lipoprotein receptor in livers of rabbits treated with 17 alpha-ethinyl estradiol. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Russell,et al.  The human LDL receptor: A cysteine-rich protein with multiple Alu sequences in its mRNA , 1984, Cell.

[12]  T. Südhof,et al.  Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[13]  R. Palmiter,et al.  Metallothionein-human GH fusion genes stimulate growth of mice. , 1983, Science.

[14]  M. Brown,et al.  Receptor-mediated endocytosis of low-density lipoprotein in cultured cells. , 1983, Methods in enzymology.

[15]  R. Palmiter,et al.  Germ-line transformation of mice. , 1986, Annual review of genetics.

[16]  L. M. Roman,et al.  A domain-specific marker for the hepatocyte plasma membrane: localization of leucine aminopeptidase to the bile canalicular domain , 1983, The Journal of cell biology.

[17]  R. Palmiter,et al.  Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Palmiter,et al.  A practical approach for quantitating specific mRNAs by solution hybridization. , 1983, Analytical biochemistry.

[19]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[20]  M R Gross,et al.  Aquatic Productivity and the Evolution of Diadromous Fish Migration , 1988, Science.

[21]  R. Palmiter,et al.  Partial correction of murine hereditary growth disorder by germ-line incorporation of a new gene , 1984, Nature.

[22]  D. Russell,et al.  mRNA for low density lipoprotein receptor in brain and spinal cord of immature and mature rabbits. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. D. Capra,et al.  Use of antipeptide antibodies to demonstrate external orientation of the NH2-terminus of the low density lipoprotein receptor in the plasma membrane of fibroblasts , 1983, The Journal of cell biology.

[24]  Michael G. Rosenfeld,et al.  Dramatic growth of mice that develop from eggs microinjected with metallothionein–growth hormone fusion genes , 1982, Nature.

[25]  P. Forgez,et al.  Distribution and Characterization of the Serum Lipoproteins and Apoproteins in the Mouse, Mus Musculus , 2022 .