Immunosuppression of Myostatin with Hepatitis B Surface Antigen S Gene As DNA Vaccine Carrier for Myosatin C-Terminal Domain cDNA Increases Muscle Mass in Female Mice and Sheep

Myostatin, a member of the TGF-β superfamily, negatively regulates skeletal muscle growth in most livestock animals. Depression or knockout of myostatin activity leads to significant muscle mass gain. In an attempt to down-regulate myostatin activity in the early stage of skeletal muscle development, we constructed a DNA vaccine plasmid by using hepatitis B surface antigen (HBsAg) S gene as a carrier for expressing myostatin C-terminal mature domain (amino acid 267–375) cDNA, namely the pV-SM vector. Intramuscular administration of pV-SM vectors in female mice and sheep were conducted in the early stage of skeletal muscle growth. The recombinant myostatin was detected by ELISA in the serum of mice and sheep since there were significant increases in myostain concentration in the treatment group compared with the control group. Improvements of growth performances were observed in both animal species with 5% heavies in body weight in the treated mice trans controls two months after administration. Muscle mass were significantly higher by 30% in the treated mice than the controls while the sheep carcass increased by 13%. The data from muscle histology suggests myofiber hypertrophy occurred in the vaccinated animals since myofiber cross-sectional area were much larger in both species in comparison with their control groups. Gene expression analysis on muscle tissue by qPCR indicates myogenine, MyoD and Myf5 levels are significantly higher (P<0.01) in treated mice than control mice, and there are decreased levels of myostatin mRNA in the vaccinated sheep. These results demonstrated effective DNA vaccine immune-suppression of myostatin activity by using HBsAg S gene as a carrier for expressing recombinant mature myostatin in mice and sheep, which improve animal growth and muscle mass.