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PMID: 8464893 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholesterol clearance in normal mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 7 ·1993-04-01 ·Pages 2812-6

Herz J, Gerard RD

Abstract

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.

MeSH Terms
Adenoviridae/genetics Animals CHO Cells Cholesterol/metabolism Cricetinae Humans Lipoproteins, LDL/blood,metabolism,pharmacokinetics Luciferases/genetics,metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Organ Specificity Receptors, LDL/genetics,metabolism Recombinant Fusion Proteins/metabolism Tissue Distribution Transfection beta-Galactosidase/genetics,metabolism
Chemicals
Lipoproteins, LDL Receptors, LDL Recombinant Fusion Proteins Cholesterol Luciferases beta-Galactosidase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Herz J
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Gerard R D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.7.2812
Published
1993-04-01
Pages
2812-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46186
Subset
IM
Grants
NHLBI NIH HHS · HL 17669 · United States
NHLBI NIH HHS · HL 20948 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.7.2812 PMC Full Text View journal details
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