Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholesterol clearance in normal mice.
We have explored the use of adenovirus-mediated gene transfer to transiently elicit production of low density lipoprotein (LDL) receptors in mice. A recombinant adenovirus carrying the human LDL receptor cDNA restored LDL receptor function in receptor-deficient cultured cells. Intravenous injection of recombinant virus acutely lowered plasma cholesterol levels and increased the rate of 125I-labeled LDL clearance from the circulation in normal mice. At 4 days after virus injection, the t1/2 of plasma LDL was reduced up to 10-fold. An estimated 90% of the parenchymal cells in liver expressed the adenovirus-transferred genes as judged by immunofluorescence of LDL receptors or by beta-galactosidase staining. These results demonstrate that adenovirus-mediated transfer of the LDL receptor gene provides an efficient way of augmenting LDL receptor gene function in the liver over the short term.
Herz
J
J
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Gerard
R D
RD
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; D002784:Cholesterol; D008156:Luciferases; D001616:beta-Galactosidase