Expression and regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice

Min Ling Liu, Ann Louise Olson, W. Scott Moye-Rowley, John B. Buse, Graeme I. Bell, Jeffrey E. Pessin

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

To study the molecular basis of tissue-specific expression of the GLUT4/muscle-fat facilitative glucose transporter gene, we generated lines of transgenic mice carrying 2.4 kilobases of the 5′-flanking region of the human GLUT4 gene fused to a chloramphenicol acetyltransferase (CAT) reporter gene (hGLUT4[2.4]-CAT). This reporter gene construct was specifically expressed in tissues that normally express GLUT4 mRNA, which include both brown and white adipose tissues as well as cardiac, skeletal, and smooth muscle. In contrast, CAT reporter activity was not detected in brain or liver, two tissues that do not express the GLUT4 gene. In addition, the relative levels of CAT mRNA driven by the human GLUT4 promoter in various tissues of these transgenic animals mirrored those of the endogenous mouse GLUT4 mRNA. Since previous studies have observed alterations in GLUT4 mRNA levels induced by fasting and refeeding (Sivitz, W. I., DeSautel, S. L., Kayano, T., Bell, G. I., and Pessin, J. E. (1989) Nature 340, 72-74), the regulated expression the hGLUT4[2.4]-CAT transgene was also assessed in these animals. Fasting was observed to decrease CAT activity in white adipose tissue which was super-induced upon refeeding. These alterations in CAT expression occurred in parallel to the changes in endogenous mouse GLUT4 mRNA levels. Although CAT expression in skeletal muscle and brown adipose tissue was unaffected, the endogenous mouse GLUT4 mRNA was also refractory to the effects of fasting/refeeding in these tissues. These data demonstrate that 2.4 kilobases of the 5′-flanking region of the human GLUT4 gene contain all the necessary sequence elements to confer tissue-specific expression and at least some of the sequence elements controlling the hormonal/metabolic regulation of this gene.

Original languageEnglish (US)
Pages (from-to)11673-11676
Number of pages4
JournalJournal of Biological Chemistry
Volume267
Issue number17
StatePublished - Jun 15 1992
Externally publishedYes

Fingerprint

Chloramphenicol O-Acetyltransferase
Facilitative Glucose Transport Proteins
Transgenic Mice
Muscle
Genes
Fats
Tissue
Muscles
Messenger RNA
Fasting
White Adipose Tissue
Brown Adipose Tissue
5' Flanking Region
Reporter Genes
Skeletal Muscle
Animals
Genetically Modified Animals
Transgenes
Smooth Muscle
Liver

ASJC Scopus subject areas

  • Biochemistry

Cite this

Expression and regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice. / Liu, Min Ling; Olson, Ann Louise; Moye-Rowley, W. Scott; Buse, John B.; Bell, Graeme I.; Pessin, Jeffrey E.

In: Journal of Biological Chemistry, Vol. 267, No. 17, 15.06.1992, p. 11673-11676.

Research output: Contribution to journalArticle

Liu, Min Ling ; Olson, Ann Louise ; Moye-Rowley, W. Scott ; Buse, John B. ; Bell, Graeme I. ; Pessin, Jeffrey E. / Expression and regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 17. pp. 11673-11676.
@article{e54755285c194337b16fa954d5f4697b,
title = "Expression and regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice",
abstract = "To study the molecular basis of tissue-specific expression of the GLUT4/muscle-fat facilitative glucose transporter gene, we generated lines of transgenic mice carrying 2.4 kilobases of the 5′-flanking region of the human GLUT4 gene fused to a chloramphenicol acetyltransferase (CAT) reporter gene (hGLUT4[2.4]-CAT). This reporter gene construct was specifically expressed in tissues that normally express GLUT4 mRNA, which include both brown and white adipose tissues as well as cardiac, skeletal, and smooth muscle. In contrast, CAT reporter activity was not detected in brain or liver, two tissues that do not express the GLUT4 gene. In addition, the relative levels of CAT mRNA driven by the human GLUT4 promoter in various tissues of these transgenic animals mirrored those of the endogenous mouse GLUT4 mRNA. Since previous studies have observed alterations in GLUT4 mRNA levels induced by fasting and refeeding (Sivitz, W. I., DeSautel, S. L., Kayano, T., Bell, G. I., and Pessin, J. E. (1989) Nature 340, 72-74), the regulated expression the hGLUT4[2.4]-CAT transgene was also assessed in these animals. Fasting was observed to decrease CAT activity in white adipose tissue which was super-induced upon refeeding. These alterations in CAT expression occurred in parallel to the changes in endogenous mouse GLUT4 mRNA levels. Although CAT expression in skeletal muscle and brown adipose tissue was unaffected, the endogenous mouse GLUT4 mRNA was also refractory to the effects of fasting/refeeding in these tissues. These data demonstrate that 2.4 kilobases of the 5′-flanking region of the human GLUT4 gene contain all the necessary sequence elements to confer tissue-specific expression and at least some of the sequence elements controlling the hormonal/metabolic regulation of this gene.",
author = "Liu, {Min Ling} and Olson, {Ann Louise} and Moye-Rowley, {W. Scott} and Buse, {John B.} and Bell, {Graeme I.} and Pessin, {Jeffrey E.}",
year = "1992",
month = "6",
day = "15",
language = "English (US)",
volume = "267",
pages = "11673--11676",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "17",

}

TY - JOUR

T1 - Expression and regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice

AU - Liu, Min Ling

AU - Olson, Ann Louise

AU - Moye-Rowley, W. Scott

AU - Buse, John B.

AU - Bell, Graeme I.

AU - Pessin, Jeffrey E.

PY - 1992/6/15

Y1 - 1992/6/15

N2 - To study the molecular basis of tissue-specific expression of the GLUT4/muscle-fat facilitative glucose transporter gene, we generated lines of transgenic mice carrying 2.4 kilobases of the 5′-flanking region of the human GLUT4 gene fused to a chloramphenicol acetyltransferase (CAT) reporter gene (hGLUT4[2.4]-CAT). This reporter gene construct was specifically expressed in tissues that normally express GLUT4 mRNA, which include both brown and white adipose tissues as well as cardiac, skeletal, and smooth muscle. In contrast, CAT reporter activity was not detected in brain or liver, two tissues that do not express the GLUT4 gene. In addition, the relative levels of CAT mRNA driven by the human GLUT4 promoter in various tissues of these transgenic animals mirrored those of the endogenous mouse GLUT4 mRNA. Since previous studies have observed alterations in GLUT4 mRNA levels induced by fasting and refeeding (Sivitz, W. I., DeSautel, S. L., Kayano, T., Bell, G. I., and Pessin, J. E. (1989) Nature 340, 72-74), the regulated expression the hGLUT4[2.4]-CAT transgene was also assessed in these animals. Fasting was observed to decrease CAT activity in white adipose tissue which was super-induced upon refeeding. These alterations in CAT expression occurred in parallel to the changes in endogenous mouse GLUT4 mRNA levels. Although CAT expression in skeletal muscle and brown adipose tissue was unaffected, the endogenous mouse GLUT4 mRNA was also refractory to the effects of fasting/refeeding in these tissues. These data demonstrate that 2.4 kilobases of the 5′-flanking region of the human GLUT4 gene contain all the necessary sequence elements to confer tissue-specific expression and at least some of the sequence elements controlling the hormonal/metabolic regulation of this gene.

AB - To study the molecular basis of tissue-specific expression of the GLUT4/muscle-fat facilitative glucose transporter gene, we generated lines of transgenic mice carrying 2.4 kilobases of the 5′-flanking region of the human GLUT4 gene fused to a chloramphenicol acetyltransferase (CAT) reporter gene (hGLUT4[2.4]-CAT). This reporter gene construct was specifically expressed in tissues that normally express GLUT4 mRNA, which include both brown and white adipose tissues as well as cardiac, skeletal, and smooth muscle. In contrast, CAT reporter activity was not detected in brain or liver, two tissues that do not express the GLUT4 gene. In addition, the relative levels of CAT mRNA driven by the human GLUT4 promoter in various tissues of these transgenic animals mirrored those of the endogenous mouse GLUT4 mRNA. Since previous studies have observed alterations in GLUT4 mRNA levels induced by fasting and refeeding (Sivitz, W. I., DeSautel, S. L., Kayano, T., Bell, G. I., and Pessin, J. E. (1989) Nature 340, 72-74), the regulated expression the hGLUT4[2.4]-CAT transgene was also assessed in these animals. Fasting was observed to decrease CAT activity in white adipose tissue which was super-induced upon refeeding. These alterations in CAT expression occurred in parallel to the changes in endogenous mouse GLUT4 mRNA levels. Although CAT expression in skeletal muscle and brown adipose tissue was unaffected, the endogenous mouse GLUT4 mRNA was also refractory to the effects of fasting/refeeding in these tissues. These data demonstrate that 2.4 kilobases of the 5′-flanking region of the human GLUT4 gene contain all the necessary sequence elements to confer tissue-specific expression and at least some of the sequence elements controlling the hormonal/metabolic regulation of this gene.

UR - http://www.scopus.com/inward/record.url?scp=0026704159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026704159&partnerID=8YFLogxK

M3 - Article

VL - 267

SP - 11673

EP - 11676

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 17

ER -