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Titolo:
Evaluation of the role of lipoprotein metabolism genes in systemic cationic liposome-mediated gene transfer in vivo
Autore:
Mounkes, LC; Zhong, W; De Silva, HV; Handumrongkul, C; Desai, B; Tse, E; Taylor, JM; Debs, RJ;
Indirizzi:
Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94115 USA Calif PacificMed Ctr San Francisco CA USA 94115 Francisco, CA 94115 USA Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA Univ N Carolina Charlotte NC USA 28223 Dept Biol, Charlotte, NC 28223 USA Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, Cardiovasc Res Inst, San Francisco, CA 94141 USA Univ Calif San Francisco San Francisco CA USA 94141 ancisco, CA 94141 USA Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94141 USA Univ Calif San Francisco San Francisco CA USA 94141 ancisco, CA 94141 USA
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 16, volume: 12, anno: 2001,
pagine: 1939 - 1954
SICI:
1043-0342(200111)12:16<1939:EOTROL>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR-RELATED PROTEIN; APOLIPOPROTEIN-A-I; TRANSGENIC MICE; CELL-SURFACE; DEFICIENT MICE; KNOCKOUT MICE; DELIVERY; CHOLESTEROL; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Debs, RJ Calif Pacific Med Ctr, Res Inst, 2330 Clay St,Stern Bldg, San Francisco, CA 94115 USA Calif Pacific Med Ctr 2330 Clay St,Stern Bldg San Francisco CA USA 94115
Citazione:
L.C. Mounkes et al., "Evaluation of the role of lipoprotein metabolism genes in systemic cationic liposome-mediated gene transfer in vivo", HUM GENE TH, 12(16), 2001, pp. 1939-1954

Abstract

Germ line gene disruption and gene insertion are often used to study the function of selected genes in vivo. We used selected knockout and transgenicmouse models to attempt to identify lipoprotein-related genes and gene products that regulate the process of intravenous cationic liposome-DNA complex (CLDC)-based gene delivery. Several observations suggested that proteins involved in lipoprotein metabolism might be important in influencing the delivery and/or expression of CLDC. First, in vitro transfection of either K562 or CHO cells by CLDCs was enhanced by the presence of a functional low-density lipoprotein receptor (LDLR). Second, pretreatment of mice with 4-aminopyrazolopyrimidine (4APP), an agent that alters lipoprotein profiles in mice, significantly decreased expression of luciferase (luc) after intravenous injection of CLDC-luc complexes in mice. Therefore, we tested mouse model systems either deficient for, or overexpressing, selected genes involved in lipoprotein metabolism, for their potential to regulate intravenous, CLDC-based gene delivery. Although homozygous knockout mutation in the apoE gene caused a significant decrease in gene expression in many tissues of apoE-deficient mice, mice with homozygous deletion of both the apoE and LDLR genes showed wild-type levels of gene transfer efficiency. Thus, a secondary event, produced by homozygous deletion of apoE, but compensated for by the concomitant deletion of LDLR, and/or effects resulting from strain-related,genetic background differences, appeared to play a significant role in mediating intravenous, CLDC-based gene delivery. Secondary alterations resulting from germ line knockouts, as well as epigenetic effects produced by strain differences, may limit the ability to assign specific, gene transfer-related functions to the deleted gene.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 14:10:55