TY - JOUR
T1 - Transcriptional regulation of the human GLUT4 gene promoter in diabetic transgenic mice
AU - Olson, Ann Louise
AU - Pessin, Jeffery E.
PY - 1995/10/6
Y1 - 1995/10/6
N2 - We previously reported that 2400 base pairs (bp) of 5'-flanking DNA is sufficient for tissue-specific and hormonal/metabolic regulation of the human GLUT4 gene in transgenic mice (Liu, M.-L., Olson, A.L., Moye-Rowley, W.S., Buse, J. B., Bell, G. I., and Pessin,, J. E. (1992) J. Biol. Chem. 267, 11673-11676). To further define the DNA sequences required for GLUT4 expression, we generated transgenic mice carrying 1975, 1639, 1154, 730, and 412 bp of the GLUT4 5'-flank (hG4) fused to the chloramphenicol acetyltransferase (CAT) reporter gene. The 1975-hG4-CAT, 1639-hG4-CAT, and 1154-hG4-CAT constructs were expressed in a tissue-specific manner identical to the endogenous murine GLUT4 mRNA. Regulation of these reporter gene constructs in insulin-deficient diabetes also paralleled the endogenous gene. In contrast, 730-hG4-CAT was expressed at high levels only in skeletal muscle and at low levels in all of the other tissues examined. Additionally, expression of 412-hG4-CAT was completely unrestricted. Neither the 730-hG4- CAT nor the 412-hG4-CAT reporter genes displayed any insulin-dependent regulation. These data demonstrate that a skeletal muscle-specific DNA element is located within 730 bp of the GLUT4 5'-flanking DNA but that 1154 bp is necessary to direct the full extent of tissue-specific and insulin- dependent regulation of the human GLUT4 gene in transgenic mice.
AB - We previously reported that 2400 base pairs (bp) of 5'-flanking DNA is sufficient for tissue-specific and hormonal/metabolic regulation of the human GLUT4 gene in transgenic mice (Liu, M.-L., Olson, A.L., Moye-Rowley, W.S., Buse, J. B., Bell, G. I., and Pessin,, J. E. (1992) J. Biol. Chem. 267, 11673-11676). To further define the DNA sequences required for GLUT4 expression, we generated transgenic mice carrying 1975, 1639, 1154, 730, and 412 bp of the GLUT4 5'-flank (hG4) fused to the chloramphenicol acetyltransferase (CAT) reporter gene. The 1975-hG4-CAT, 1639-hG4-CAT, and 1154-hG4-CAT constructs were expressed in a tissue-specific manner identical to the endogenous murine GLUT4 mRNA. Regulation of these reporter gene constructs in insulin-deficient diabetes also paralleled the endogenous gene. In contrast, 730-hG4-CAT was expressed at high levels only in skeletal muscle and at low levels in all of the other tissues examined. Additionally, expression of 412-hG4-CAT was completely unrestricted. Neither the 730-hG4- CAT nor the 412-hG4-CAT reporter genes displayed any insulin-dependent regulation. These data demonstrate that a skeletal muscle-specific DNA element is located within 730 bp of the GLUT4 5'-flanking DNA but that 1154 bp is necessary to direct the full extent of tissue-specific and insulin- dependent regulation of the human GLUT4 gene in transgenic mice.
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U2 - 10.1074/jbc.270.40.23491
DO - 10.1074/jbc.270.40.23491
M3 - Article
C2 - 7559512
AN - SCOPUS:0028859475
SN - 0021-9258
VL - 270
SP - 23491
EP - 23495
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -