Myostatin Dominant Negative Allele Products Interact Positively with Wild Type Monomers

Myostatin is an extracellular negative regulator of muscle growth with an important role in bovine muscular hypertrophy. It belongs to the transforming growth factor (beta) (TGF(beta)) superfamily, and has structural and functional characteristics similar to those of its other members. Based on these characteristics, we designed three gene constructs in order to create a series of dominant negative (DN) alleles for murine myostatin. As a first requirement for any DN strategy, we first showed that each of the three mutant DN monomers were able to interact with wild type mature myostatin (wt-Mstn), both in a pull-down and a mammalian two-hybrid assay. In addition, the degree of DN-Mstn/wt-Mstn interaction was similar to that of wt-Mstn/wt-Mstn. These results suggest that the three designed alleles are good candidates for use in a DN-based strategy for generating muscular hypertrophy in cattle.