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Am J Physiol Cell Physiol (June 9, 2004). doi:10.1152/ajpcell.00492.2003
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Submitted on November 7, 2003
Accepted on May 31, 2004

Molecular analysis of fiber-type specific expression of murine myostatin promoter

Monica Senna Salerno1, Mark Thomas1, Davanea Forbes1, Trevor Watson1, Ravi Kambadur1, and Mridula Sharma1*

1 Animal Genomics, AgResearch, Hamilton, New Zealand; Ovita Ltd., Dunedin, New Zealand

* To whom correspondence should be addressed. E-mail: mridula.sharma{at}agresearch.co.nz.

Myostatin is a negative regulator of muscle growth, and absence of the functional myostatin protein leads to heavy muscle phenotype in both mouse and cattle. Although the role of myostatin in controlling muscle mass is established, little is known of the mechanisms regulating the expression of the myostatin gene. In this study, we have characterised the murine myostatin promoter in vivo. Various constructs of the murine myostatin promoter were injected into the quadriceps muscle of mice, and the reporter luciferase activity was analysed. The results indicate that of the 7 E-boxes present in the 2.5kb fragment of the murine myostatin promoter, E5 E-box plays an important role in the regulation of the promoter activity in vivo. Furthermore, the in vitro studies demonstrated that MyoD preferentially binds and upregulates the murine myostatin promoter activity. We also analysed the activity of the bovine and murine promoters in mouse skeletal muscle and show that, despite displaying comparable levels of activity in murine myoblast cultures, the bovine myostatin promoter activity is much weaker in mice as compared to murine myostatin promoter. Finally, we demonstrate that in vivo, the 2.5kb region of the murine myostatin promoter is sufficient to drive the activity of the reporter gene in a fiber-type specific manner.




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