TY - JOUR
T1 - Regulated expression of 5'-deleted mouse GLUT4 minigenes in transgenic mice
T2 - Effects of exercise training and high-fat diet
AU - Tsunoda, Nobuyo
AU - Cooke, David W.
AU - Ikemoto, Shinji
AU - Maruyama, Kayo
AU - Takahashi, Mayumi
AU - Lane, M. Daniel
AU - Ezaki, Osamu
N1 - Funding Information:
We are grateful to M. Koda and M. Kurumiya for excellent technical assistance. This work was supported by research grants from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (Washington, DC), the Japanese Ministry of Health and Welfare, the Japanese Ministry of Education, Science and Culture (Tokyo), and the Japanese Science and Technology Agency (Tokyo).
PY - 1997/10/20
Y1 - 1997/10/20
N2 - Fourteen kb murine GLUT4 minigene (= -7395 GLUT4) contains DNA sequence that confers tissue specific, exercise-induced up-regulation of the GLUT4 gene in skeletal muscle and high-fat diet induced-down-regulation in white adipose tissue. To identify the DNA sequences required for regulated expression, we generated GLUT4 minigene transgenic mice harboring 3237, 2000, 1000, and 442 bp of 5'-flanking region, all exons and introns, and 1 kb of 3'-flanking sequence of the mouse GLUT4 gene. The -3237-, -2000-, and -1000-GLUT4 constructs were expressed in a tissue-specific manner identical to the endogenous GLUT4. Exercise-induced up-regulation and high-fat diet-induced down-regulation of these constructs also paralleled those of the endogenous GLUT4 gene. In contrast, the -442 GLUT4 construct was expressed substantially in skeletal muscle (gastrocnemius and quadriceps) and heart, but was only expressed very weakly in white adipose tissue and was not expressed in brown adipose tissue. Furthermore, this -442 GLUT4 construct failed to respond to exercise or a high-fat diet in either muscle or adipose tissue. These results indicate that brown and white adipocyte-specific enhancer(s) and exercise- and high-fat diet-responsive elements are located between bases -1000 and -442 of the murine GLUT4 5'-flanking re -gion.
AB - Fourteen kb murine GLUT4 minigene (= -7395 GLUT4) contains DNA sequence that confers tissue specific, exercise-induced up-regulation of the GLUT4 gene in skeletal muscle and high-fat diet induced-down-regulation in white adipose tissue. To identify the DNA sequences required for regulated expression, we generated GLUT4 minigene transgenic mice harboring 3237, 2000, 1000, and 442 bp of 5'-flanking region, all exons and introns, and 1 kb of 3'-flanking sequence of the mouse GLUT4 gene. The -3237-, -2000-, and -1000-GLUT4 constructs were expressed in a tissue-specific manner identical to the endogenous GLUT4. Exercise-induced up-regulation and high-fat diet-induced down-regulation of these constructs also paralleled those of the endogenous GLUT4 gene. In contrast, the -442 GLUT4 construct was expressed substantially in skeletal muscle (gastrocnemius and quadriceps) and heart, but was only expressed very weakly in white adipose tissue and was not expressed in brown adipose tissue. Furthermore, this -442 GLUT4 construct failed to respond to exercise or a high-fat diet in either muscle or adipose tissue. These results indicate that brown and white adipocyte-specific enhancer(s) and exercise- and high-fat diet-responsive elements are located between bases -1000 and -442 of the murine GLUT4 5'-flanking re -gion.
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U2 - 10.1006/bbrc.1997.7516
DO - 10.1006/bbrc.1997.7516
M3 - Article
C2 - 9344860
AN - SCOPUS:0031581093
SN - 0006-291X
VL - 239
SP - 503
EP - 509
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -