Transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apoVLDL-II expression in transgenic mice

We have produced transgenic mice that express an estrogen-responsive avian apolipoprotein, apoVLDL-II. An apoVLDL-II natural gene construct containing 4.7 kb of 5‘ flanking and 19 bp of 3‘ flanking sequences together with the 4 exon/3 intron structural gene was expressed in a liver-specific manner i...

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Main Authors: E Zsigmond, M K Nakanishi, F E Ghiselli, L Chan
Format: Article
Language:English
Published: Elsevier 1995-07-01
Series:Journal of Lipid Research
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520397327
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spelling doaj-58f06625b7f444eebf213c9a8c5901702021-04-26T05:50:01ZengElsevierJournal of Lipid Research0022-22751995-07-0136714531462Transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apoVLDL-II expression in transgenic miceE Zsigmond0M K Nakanishi1F E Ghiselli2L Chan3Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.We have produced transgenic mice that express an estrogen-responsive avian apolipoprotein, apoVLDL-II. An apoVLDL-II natural gene construct containing 4.7 kb of 5‘ flanking and 19 bp of 3‘ flanking sequences together with the 4 exon/3 intron structural gene was expressed in a liver-specific manner in transgenic mice. A single injection of estrogen caused a 5.9- to 7.5-fold stimulation of apoVLDL-II mRNA in the liver. The transgene mRNA had the same initiation sites of transcription as the native mRNA isolated from laying hen liver, and the same sites were used before and after estrogen treatment. The number of hepatocytes that stain positive for immunoreactive apoVLDL-II increased from < 1% to 40-60% in 24 h after estrogen treatment. Thus, in trangenic mice as in the cockerel, hepatocytes are biochemically heterogeneous and induction of apoVLDL-II synthesis occurs by recruitment of hepatocytes. In the plamsa compartment, compared to controls, transgenic mice have a 3- to 5-fold higher basal total plasma triglyceride which was accounted for by a 5.4-fold high basal VLDL triglyceride. Estrogen treatment results in a approximately 2-fold increase in the VLDL triglycerides over basal levels and 8.5-fold increase over nontransgenic mice, which did not show any change in VLDL in response to estrogen. Transgenic mice with the integrated apoVLDL-II gene provide a useful model for the study of the regulation of lipoprotein metabolism by estrogen.http://www.sciencedirect.com/science/article/pii/S0022227520397327
collection DOAJ
language English
format Article
sources DOAJ
author E Zsigmond
M K Nakanishi
F E Ghiselli
L Chan
spellingShingle E Zsigmond
M K Nakanishi
F E Ghiselli
L Chan
Transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apoVLDL-II expression in transgenic mice
Journal of Lipid Research
author_facet E Zsigmond
M K Nakanishi
F E Ghiselli
L Chan
author_sort E Zsigmond
title Transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apoVLDL-II expression in transgenic mice
title_short Transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apoVLDL-II expression in transgenic mice
title_full Transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apoVLDL-II expression in transgenic mice
title_fullStr Transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apoVLDL-II expression in transgenic mice
title_full_unstemmed Transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apoVLDL-II expression in transgenic mice
title_sort transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apovldl-ii expression in transgenic mice
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 1995-07-01
description We have produced transgenic mice that express an estrogen-responsive avian apolipoprotein, apoVLDL-II. An apoVLDL-II natural gene construct containing 4.7 kb of 5‘ flanking and 19 bp of 3‘ flanking sequences together with the 4 exon/3 intron structural gene was expressed in a liver-specific manner in transgenic mice. A single injection of estrogen caused a 5.9- to 7.5-fold stimulation of apoVLDL-II mRNA in the liver. The transgene mRNA had the same initiation sites of transcription as the native mRNA isolated from laying hen liver, and the same sites were used before and after estrogen treatment. The number of hepatocytes that stain positive for immunoreactive apoVLDL-II increased from < 1% to 40-60% in 24 h after estrogen treatment. Thus, in trangenic mice as in the cockerel, hepatocytes are biochemically heterogeneous and induction of apoVLDL-II synthesis occurs by recruitment of hepatocytes. In the plamsa compartment, compared to controls, transgenic mice have a 3- to 5-fold higher basal total plasma triglyceride which was accounted for by a 5.4-fold high basal VLDL triglyceride. Estrogen treatment results in a approximately 2-fold increase in the VLDL triglycerides over basal levels and 8.5-fold increase over nontransgenic mice, which did not show any change in VLDL in response to estrogen. Transgenic mice with the integrated apoVLDL-II gene provide a useful model for the study of the regulation of lipoprotein metabolism by estrogen.
url http://www.sciencedirect.com/science/article/pii/S0022227520397327
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