| First Author | Charvet C | Year | 2006 |
| Journal | Mol Cell Biol | Volume | 26 |
| Issue | 17 | Pages | 6664-74 |
| PubMed ID | 16914747 | Mgi Jnum | J:112113 |
| Mgi Id | MGI:3655552 | Doi | 10.1128/MCB.00138-06 |
| Citation | Charvet C, et al. (2006) New role for serum response factor in postnatal skeletal muscle growth and regeneration via the interleukin 4 and insulin-like growth factor 1 pathways. Mol Cell Biol 26(17):6664-74 |
| abstractText | Serum response factor (SRF) is a crucial transcriptional factor for muscle-specific gene expression. We investigated SRF function in adult skeletal muscles, using mice with a postmitotic myofiber-targeted disruption of the SRF gene. Mutant mice displayed severe skeletal muscle mass reductions due to a postnatal muscle growth defect resulting in highly hypotrophic adult myofibers. SRF-depleted myofibers also failed to regenerate following injury. Muscles lacking SRF had very low levels of muscle creatine kinase and skeletal alpha-actin (SKA) transcripts and displayed other alterations to the gene expression program, indicating an overall immaturity of mutant muscles. This loss of SKA expression, together with a decrease in beta-tropomyosin expression, contributed to myofiber growth defects, as suggested by the extensive sarcomere disorganization found in mutant muscles. However, we observed a downregulation of interleukin 4 (IL-4) and insulin-like growth factor 1 (IGF-1) expression in mutant myofibers which could also account for their defective growth and regeneration. Indeed, our demonstration of SRF binding to interleukin 4 and IGF-1 promoters in vivo suggests a new crucial role for SRF in pathways involved in muscle growth and regeneration. |
