Abstract：Myostatin (MSTN), also known as GDF-8 (growth-differentiation factor 8), is a member of the transforming growth factor-beta (TGF-β) super-family, which participates in various process of body growth regulation. As a negative regulatory of muscle growth, its mutation will lead to the excessive proliferation of muscle cells and muscle hypertrophy. To study how MSTN mutation affect its protein structure and biology functions, the multi-level structure and function changes of MSTN were predicted and analyzed by bioinformatics methods, based on our MSTN gene knock-out mice (Mus musculus). The results showed that the nt 175~180 sequence in the third exon of the MSTN gene was missing, the expression level of the MSTN decreased which led to deprived the MSTN protein in muscle, the expression level of myogenin determination gene (Myod), myogenic factor 5 gene (Myf5) and myogenin gene (Myog) increased significantly, activin typeⅡreceptor b3 gene (ActR2b3), the receptor protein of the MSTN decreased and the muscle hypertrophy. Analysis of the deletion mutation MSTN protein structure, it lost the Y (309) and C(310) amino acids, which elongated the beta pleated sheet and changed the protein structure. The functional prediction result showed that, the mutant MTSN protein of these mice lost a protein bonding site, which reduced its bonding capability to the receptor and impaired its biological functions. This study showed that the third exon nt 175~180 of MSTN in mice was the core sequence that affected the function of MSTN protein, and resulted in the muscle hypertrophy phenotype, which would provide a good mouse model for studying the function of MSTN gene.
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