Myogenic Vector Expression of Insulin-like Growth Factor I Stimulates Muscle Cell Differentiation and Myofiber Hypertrophy in Transgenic Mice
Open accessAbstract
The avian skeletal alpha-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 alpha-actin gene directed high level expression of human insulin-like growth factor I (IGF-I) in stably transfected C2C12 myoblasts and transgenic mice. Expression of the actin/IGF-I hybrid gene in C2C12 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 alpha-actin-based vectors.
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In animal models, mTORC1 activation by animal-specific resistance training, IGF-1, or Akt1 expression causes muscle hypertrophy.
“In animal models, mTORC1 activation either by animal-specific resistance training, IGF-1 [36], or Akt1 expression [37] causes muscle hypertrophy.”
From Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search (2025) · cites this paper as [36]
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- Authors
- Coleman, M. E., DeMayo, F., Yin, K. C., Lee, H. M., Geske, R., Montgomery, C., & Schwartz, R. J.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Schwartz, Robert J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-05
- Volume
- 270
- Issue
- 20
- Pages
- 12109-12116
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2055492254
- Cited by
- 642
- References
- 52
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 13 · 2021: 25 · 2020: 11 · 2019: 15 · 2018: 22 · 2017: 11 · 2016: 18 · 2015: 26 · 2014: 26 · 2013: 28 · 2012: 25
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (T32AG000183)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- insulin-like growth factor I, transgenic mice, skeletal muscle hypertrophy, muscle cell differentiation, myotube formation, C2C12 myoblasts, bHLH transcription factors
- MeSH terms
- Actins, Animals, Cell Differentiation, Cell Fusion, Cells, Cultured, Female, Gene Expression Regulation, Genes, Synthetic, Genetic Vectors, Hypertrophy, Insulin-Like Growth Factor I, Male, Mice, Transgenic, Muscle Proteins, Muscles, Organ Specificity, Promoter Regions, Genetic, Recombinant Fusion Proteins, RNA, Messenger, Transfection, Helix-Loop-Helix Motifs, Muscle Fibers, Skeletal, Mice
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