Regulation of muscle growth in teleost fish by members of the transforming growth factor beta superfamily

Little is known of the mechanisms regulating the growth and development of muscle tissue in teleost fish. Mammalian muscle growth is negatively regulated by multiple signaling proteins of the transforming growth factor beta superfamily (TGF-beta), including myostatin. Teleost myostatin genes have high protein sequence conservation with the mammalian myostatin gene however, the levels of myostatin expression and tissue distribution as well as the overall muscle structure of fish and mammals, differ significantly. To determine whether TGF-beta signaling is required for proper muscle growth and development in fish, two strains of transgenic rainbow trout (RBT; Oncorhynchus mykiss (Walbaum)) were produced overexpressing a broad TGF-beta or myostatin specific inhibitor in muscle tissue.;Transgenic RBT overexpressing a non-functional myostatin molecule (C311Y) exhibited normal muscle development. One microinjection cohort of transgenic fish exhibited a possible correlation between growth (i.e., weight and length) and C311Y expression. There was no difference in weight, length, condition factor or morphology in the C311Y F1 generation, however large P1 individuals did not produce offspring in the first spawning season.;It remains unclear which TGF-beta molecules are primarily responsible for the "six pack" phenotype, since the phenotype was not observed in C311Y transgenic fish. It is possible that a higher level of C311Y expression (e.g., homozygotes) is required to induce a phenotypic response to myostatin inhibition in trout. Alternatively, the lack of "six pack" muscling in C311Y transgenic RBT may suggest that myostatin has a limited role in regulating muscle growth in fish.;Broad TGF-beta inhibition, through overexpression of a truncated zebrafish Activin receptor IIB (tActRIIB) caused significant muscle growth in localized regions of the epaxial and abdominal musculature. This "six pack" phenotype is similar to that observed with follistatin overexpression in RBT. Several F1 fish from two tActRIIB transgenic lines were significantly larger than controls in both weight and condition factor and exhibited a phenotype reminiscent of double muscled mammals.