Enhanced Myogenesis in adult skeletal muscle by transgenic expression of Myostatin Propeptide

Authors: ZHAO, BAOPING - UNIVERSITY OF HAWAII; LI, ELILENNA - UNIVERSITY OF HAWAII; Wall, Robert; YANG, JINZENG - UNIVERSITY OF HAWAII

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/23/2009
Publication Date: 7/8/2009
Citation: Zhao, B., Li, E.J., Wall, R.J., Yang, J. 2009. Enhanced Myogenesis in adult skeletal muscle by transgenic expression of Myostatin Propeptide. Biomed Central (BMC) Genomics 2009, 10:305 doi:10.1186/1471-2164-10-305.

Interpretive Summary: The myostatin gene plays a critical roll in controlling muscle growth during mammalian development. An animal is born with all its muscle cells and during postnatal development muscles mature by growing larger and the process is usually completed by the time an individual reaches adulthood. However, in the myostatin prodomain transgenic mice new muscle mass continues to develop through out the animals life. We have previously shown that over expressing the propeptide domain of myostatin we can enhance muscle growth in young animals. The study reported here focused on evaluating the influence of myostatin prodomain later in life. We looked into how the transgene was causing continuous growth and found that expression of endogenous genes which serve as myogenic regulators was enhanced as were genes encoding extracellular matrix proteins in transgenic animals as apposed to controls. In addition, genes associated with protein degradation were turned down. These results provide a basic understanding of the genome wide influence of myostatin’s mode of action and should serve as a guide for using anti-myostatin therapies in muscular dystrophy patients and in enhancing growth in swine.

Technical Abstract: Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-ß, plays a dominant role in the genetic control of muscle mass. Transgenic expression of myostatin propeptide in skeletal muscle showed dramatic growth and muscle mass in young mice. To further characterize muscle growth in later stages of life, we reported 76-152% significant enhancements of main individual muscle mass over the wild-type littermate mice and continuous myogenesis by myostatin propeptide at 12 months of age. Active myogenesis in adult skeletal muscle was demonstrated by a large number of nuclei localized in the central and basal lamina of the myofibers of the transgenic mice as the number of nuclei per fiber and 100 µm2 area was significantly higher in transgenic mice than wild-type mice. By systemic comparisons of global mRNA expression patterns between transgenic mice and wild-type littermates, we have identified distinct gene expression patterns to support adult myogenesis, which are comprised of enhanced expressions of myogenic regulatory factors and extracellular matrix components, and differentially down regulated expressions of genes related to protein degradation and mitochondrial ATP synthesis. Enhanced myogenesis in adult muscle is sustained by reduced ATP synthesis as a result of a decreased activity of protein degradation. The results present a distinct coordinated pattern of gene expressions for reduced energy utilization during adult myogenesis by myostatin propeptide.