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Updated: Aug 20, 2026
Chromatin Immunoprecipitation Assay for Tissue-specific Genes using Early-stage Mouse Embryos
Published on: April 29, 2011
Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene
Shijie Li1, Michael P Czubryt, John McAnally
1Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
Abstract:
Serum response factor (SRF) controls the transcription of muscle genes by recruiting a variety of partner proteins, including members of the myocardin family of transcriptional coactivators. Mice lacking SRF fail to form mesoderm and die before gastrulation, precluding an analysis of the roles of SRF in muscle tissues. To investigate the functions of SRF in skeletal muscle development, we conditionally deleted the Srf gene in mice by skeletal muscle-specific expression of Cre recombinase. In mice lacking skeletal muscle SRF expression, muscle fibers formed, but failed to undergo hypertrophic growth after birth. Consequently, mutant mice died during the perinatal period from severe skeletal muscle hypoplasia. The myopathic phenotype of these mutant mice resembled that of mice expressing a dominant negative mutant of a myocardin family member in skeletal muscle. These findings reveal an essential role for the partnership of SRF and myocardin-related transcription factors in the control of skeletal muscle growth and maturation in vivo.
Insights
Serum response factor (SRF) is crucial for skeletal muscle growth. Conditional deletion of SRF in mice led to muscle hypoplasia and perinatal death, highlighting its essential role in muscle maturation.
Area of Science:
- Muscle development
- Transcriptional regulation
- Developmental biology
Background:
- Serum response factor (SRF) regulates muscle gene transcription via coactivators like myocardin family members.
- Global SRF knockout mice are embryonic lethal before mesoderm formation, preventing study of SRF in muscle tissues.
Purpose of the Study:
- To investigate the specific role of SRF in skeletal muscle development and growth in vivo.
- To elucidate the function of SRF-myocardin partnerships in postnatal muscle maturation.
Main Methods:
- Conditional deletion of the Srf gene in adult mice using skeletal muscle-specific Cre recombinase.
- Analysis of skeletal muscle morphology, growth, and survival in mutant mice.
- Comparison of phenotypes with mice expressing dominant-negative myocardin mutants.
Main Results:
- Skeletal muscle-specific SRF deletion resulted in muscle fibers that failed to grow postnatally.
- Mutant mice exhibited severe skeletal muscle hypoplasia and died perinatally.
- The observed myopathic phenotype mimicked that of mice with impaired myocardin function.
Conclusions:
- SRF is essential for the hypertrophic growth and maturation of skeletal muscle after birth.
- The partnership between SRF and myocardin-related transcription factors is critical for skeletal muscle development in vivo.
