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Volume 270, Number 20, Issue of May 19, pp. 12109-12116, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Myogenic Vector Expression of Insulin-like Growth Factor I Stimulates Muscle Cell Differentiation and Myofiber Hypertrophy in Transgenic Mice

Michael E. Coleman , Francesco DeMayo , Kuo Chang Yin , Heung Man Lee , Robert Geske , Chuck Montgomery , Robert J. Schwartz

The avian skeletal -actin gene was used as a template for construction of a myogenic expression vector that was utilized to direct expression of a human IGF-I cDNA in cultured muscle cells and in striated muscle of transgenic mice. The proximal promoter region, together with the first intron and 1.8 kilobases of 3`-noncoding flanking sequence of the avian skeletal -actin gene directed high level expression of human insulin-like growth factor I (IGF-I) in stably transfected CC myoblasts and transgenic mice. Expression of the actin/IGF-I hybrid gene in CC muscle cells increased levels of myogenic basic helix-loop-helix factor and contractile protein mRNAs and enhanced myotube formation. Expression of the actin/IGF-I hybrid gene in mice elevated IGF-I concentrations in skeletal muscle 47-fold resulting in myofiber hypertrophy. IGF-I concentrations in serum and body weight were not increased by transgene expression, suggesting that the effects of transgene expression were localized. These results indicate that sustained overexpression of IGF-I in skeletal muscle elicits myofiber hypertrophy and provides the basis for manipulation of muscle physiology utilizing skeletal -actin-based vectors.



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Y.-J. Kim, S. Noguchi, Y. K. Hayashi, T. Tsukahara, T. Shimizu, and K. Arahata
The product of an oculopharyngeal muscular dystrophy gene, poly(A)-binding protein 2, interacts with SKIP and stimulates muscle-specific gene expression
Hum. Mol. Genet., May 1, 2001; 10(11): 1129 - 1139.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
M. Brink, S. R. Price, J. Chrast, J. L. Bailey, A. Anwar, W. E. Mitch, and P. Delafontaine
Angiotensin II Induces Skeletal Muscle Wasting through Enhanced Protein Degradation and Down-Regulates Autocrine Insulin-Like Growth Factor I
Endocrinology, April 1, 2001; 142(4): 1489 - 1496.
[Abstract] [Full Text]

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 EndocrinologyHome page
G. Zhao, R. L. Sutliff, C. S. Weber, J. Wang, J. Lorenz, R. J. Paul, and J. A. Fagin
Smooth Muscle-Targeted Overexpression of Insulin-Like Growth Factor I Results in Enhanced Vascular Contractility
Endocrinology, February 1, 2001; 142(2): 623 - 632.
[Abstract] [Full Text] [PDF]

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 JCBHome page
M. A. Lawlor and P. Rotwein
Coordinate Control of Muscle Cell Survival by Distinct Insulin-like Growth Factor Activated Signaling Pathways
J. Cell Biol., December 4, 2000; 151(6): 1131 - 1140.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
M. A. Lawlor and P. Rotwein
Insulin-Like Growth Factor-Mediated Muscle Cell Survival: Central Roles for Akt and Cyclin-Dependent Kinase Inhibitor p21
Mol. Cell. Biol., December 1, 2000; 20(23): 8983 - 8995.
[Abstract] [Full Text]

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 Am. J. Physiol. Cell Physiol.Home page
E. E. Dupont-Versteegden, R. J. L. Murphy, J. D. Houle, C. M. Gurley, and C. A. Peterson
Mechanisms leading to restoration of muscle size with exercise and transplantation after spinal cord injury
Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1677 - C1684.
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 FASEB J.Home page
L. A. SCHILDMEYER, R. BRAUN, G. TAFFET, M. DEBIASI, A. E. BURNS, A. BRADLEY, and R. J. SCHWARTZ
Impaired vascular contractility and blood pressure homeostasis in the smooth muscle {alpha}-actin null mouse
FASEB J, November 1, 2000; 14(14): 2213 - 2220.
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 EndocrinologyHome page
M. Holzenberger, P. Leneuve, G. Hamard, B. Ducos, L. Perin, M. Binoux, and Y. Le Bouc
A Targeted Partial Invalidation of the Insulin-Like Growth Factor I Receptor Gene in Mice Causes a Postnatal Growth Deficit
Endocrinology, July 1, 2000; 141(7): 2557 - 2566.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
P. M. CORVA and J. F. MEDRANO
Diet effects on weight gain and body composition in high growth (hg/hg) mice
Physiol Genomics, June 29, 2000; 3(1): 17 - 23.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
M. A. Lawlor, X. Feng, D. R. Everding, K. Sieger, C. E. H. Stewart, and P. Rotwein
Dual Control of Muscle Cell Survival by Distinct Growth Factor-Regulated Signaling Pathways
Mol. Cell. Biol., May 1, 2000; 20(9): 3256 - 3265.
[Abstract] [Full Text]

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 Am. J. Physiol. Endocrinol. Metab.Home page
M. Fournier and M. I. Lewis
Influences of IGF-I gene disruption on the cellular profile of the diaphragm
Am J Physiol Endocrinol Metab, April 1, 2000; 278(4): E707 - E715.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
M. J. Fedele, J. M. Hernandez, C. H. Lang, T. C. Vary, S. R. Kimball, L. S. Jefferson, and P. A. Farrell
Severe diabetes prohibits elevations in muscle protein synthesis after acute resistance exercise in rats
J Appl Physiol, January 1, 2000; 88(1): 102 - 108.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
K. L. Haugk, H.-M. P. Wilson, K. Swisshelm, and L. S. Quinn
Insulin-Like Growth Factor (IGF)-Binding Protein-Related Protein-1: An Autocrine/Paracrine Factor That Inhibits Skeletal Myoblast Differentiation but Permits Proliferation in Response to IGF
Endocrinology, January 1, 2000; 141(1): 100 - 110.
[Abstract] [Full Text] [PDF]

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 ScienceHome page
C. Rommel, B. A. Clarke, S. Zimmermann, L. Nuñez, R. Rossman, K. Reid, K. Moelling, G. D. Yancopoulos, and D. J. Glass
Differentiation Stage-Specific Inhibition of the Raf-MEK-ERK Pathway by Akt
Science, November 26, 1999; 286(5445): 1738 - 1741.
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 FASEB J.Home page
M. C. DELAUGHTER, G. E. TAFFET, M. L. FIOROTTO, M. L. ENTMAN, and R. J. SCHWARTZ
Local insulin-like growth factor I expression induces physiologic, then pathologic, cardiac hypertrophy in transgenic mice
FASEB J, November 1, 1999; 13(14): 1923 - 1929.
[Abstract] [Full Text]

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 Arch Otolaryngol Head Neck SurgHome page
A. Shiotani, B. W. O'Malley Jr, M. E. Coleman, and P. W. Flint
Human Insulinlike Growth Factor 1 Gene Transfer Into Paralyzed Rat Larynx: Single vs Multiple Injection
Arch Otolaryngol Head Neck Surg, May 1, 1999; 125(5): 555 - 560.
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 J. Physiol.Home page
Z.-M. Wang, M. Laura Messi, M. Renganathan, and O. Delbono
Insulin-like growth factor-1 enhances rat skeletal muscle charge movement and L-type Ca2+ channel gene expression
J. Physiol., April 15, 1999; 516(2): 331 - 341.
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 J. Physiol.Home page
G. McKoy, W. Ashley, J. Mander, S. Y. Yang, N. Williams, B. Russell, and G. Goldspink
Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation
J. Physiol., April 15, 1999; 516(2): 583 - 592.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
A. Musaro and N. Rosenthal
Maturation of the Myogenic Program Is Induced by Postmitotic Expression of Insulin-Like Growth Factor I
Mol. Cell. Biol., April 1, 1999; 19(4): 3115 - 3124.
[Abstract] [Full Text] [PDF]

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 Arch Otolaryngol Head Neck SurgHome page
P. W. Flint, A. Shiotani, and B. W. O'Malley Jr
IGF-1 Gene Transfer Into Denervated Rat Laryngeal Muscle
Arch Otolaryngol Head Neck Surg, March 1, 1999; 125(3): 274 - 279.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Zetser, E. Gredinger, and E. Bengal
p38 Mitogen-activated Protein Kinase Pathway Promotes Skeletal Muscle Differentiation. PARTICIPATION OF THE MEF2C TRANSCRIPTION FACTOR
J. Biol. Chem., February 19, 1999; 274(8): 5193 - 5200.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
E. R. Barton-Davis, D. I. Shoturma, A. Musaro, N. Rosenthal, and H. L. Sweeney
Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function
PNAS, December 22, 1998; 95(26): 15603 - 15607.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. Renganathan, M. L. Messi, and O. Delbono
Overexpression of IGF-1 Exclusively in Skeletal Muscle Prevents Age-related Decline in the Number of Dihydropyridine Receptors
J. Biol. Chem., October 30, 1998; 273(44): 28845 - 28851.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
J.-L. Liu, A. Grinberg, H. Westphal, B. Sauer, D. Accili, M. Karas, and D. LeRoith
Insulin-Like Growth Factor-I Affects Perinatal Lethality and Postnatal Development in a Gene Dosage-Dependent Manner: Manipulation Using the Cre/loxP System in Transgenic Mice
Mol. Endocrinol., September 1, 1998; 12(9): 1452 - 1462.
[Abstract] [Full Text]

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 Am. J. Physiol. Endocrinol. Metab.Home page
D. S. Criswell, F. W. Booth, F. DeMayo, R. J. Schwartz, S. E. Gordon, and M. L. Fiorotto
Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy
Am J Physiol Endocrinol Metab, September 1, 1998; 275(3): E373 - E379.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
G. R. Adams and S. A. McCue
Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats
J Appl Physiol, May 1, 1998; 84(5): 1716 - 1722.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
E. Gredinger, A. N. Gerber, Y. Tamir, S. J. Tapscott, and E. Bengal
Mitogen-activated Protein Kinase Pathway Is Involved in the Differentiation of Muscle Cells
J. Biol. Chem., April 24, 1998; 273(17): 10436 - 10444.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
P. Kaliman, J. Canicio, P. R. Shepherd, C. A. Beeton, X. Testar, M. Palacín, and A. Zorzano
Insulin-like Growth Factors Require Phosphatidylinositol 3-Kinase to Signal Myogenesis: Dominant Negative p85 Expression Blocks Differentiation of L6E9 Muscle Cells
Mol. Endocrinol., January 1, 1998; 12(1): 66 - 77.
[Abstract] [Full Text]

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 CirculationHome page
Y. Tsurumi, S. Takeshita, D. Chen, M. Kearney, S. T. Rossow, J. Passeri, J. R. Horowitz, J. F. Symes, and J. M. Isner
Direct Intramuscular Gene Transfer of Naked DNA Encoding Vascular Endothelial Growth Factor Augments Collateral Development and Tissue Perfusion
Circulation, December 15, 1996; 94(12): 3281 - 3290.
[Abstract] [Full Text]

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 J. Appl. Physiol.Home page
G. R. Adams and F. Haddad
The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy
J Appl Physiol, December 1, 1996; 81(6): 2509 - 2516.
[Abstract] [Full Text] [PDF]


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