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Isolation and Characterization of Myostatin Complementary Deoxyribonucleic Acid Clones from Two Commercially Important Fish: Oreochromis mossambicus and Morone chrysops¹

Pediatric Endocrinology and The Ilyssa Center for Molecular and Cellular Endocrinology (B.D.R., M.A.L.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Department of Zoology (G.M.W., C.V.S.), North Carolina State University, Raleigh, North Carolina 27695

Address all correspondence and requests for reprints to: Dr. Buel D. Rodgers, Pediatric Endocrinology, The Johns Hopkins University School of Medicine, 600 North Wolf Street, Park 211, Baltimore, Maryland 21287. E-mail: drodgers{at}jhmi.edu

In mammals, skeletal muscle mass is negatively regulated by a muscle-derived growth/differentiating factor named myostatin (MSTN) that belongs to the transforming growth factor-ß superfamily. Although putative MSTN homologs have been identified from several vertebrates, nonmammalian orthologs remained poorly defined. Thus, we isolated and characterized MSTN complementary DNA clones from the skeletal muscle of the tilapia Oreochromis mossambicus and the white bass Morone chrysops. The nucleic and amino acid sequences from both fish species are highly homologous to the previously identified mammalian and avian orthologs, and both possess conserved cysteine residues and putative RXXR proteolytic processing sites that are common to all transforming growth factor-ß family members. Western blotting of conditioned medium from human embryonal kidney (HEK293) cells overexpressing a His-tagged tilapia MSTN indicates that the secreted fish protein is processed in a manner similar to mouse MSTN. However, in contrast to mice, MSTN expression in tilapia is not limited to skeletal muscle as it occurs in many tissues. Furthermore, the timing of MSTN expression in developing tilapia larvae coincides with myogenesis. These results suggest that the biological actions of MSTN in the tilapia and possibly in other fishes may not be limited to myocyte growth repression, but may additionally influence different cell types and organ systems.

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