The double mutations of acvr2aa and acvr2ba leads to muscle hypertrophy in zebrafish

Activin A receptor, type II (Acvr2) is a member of the transforming growth factor beta receptor family and can function as a negative regulator of skeletal muscle mass. Acvr2 plays an important role in regulating muscle development that can inhibit skeletal muscle growth in mice. However, there is very little research reported on the function of acvr2 in muscle development of teleost. In this study, we analyzed the effect of acvr2aa and acvr2ba on muscle development in zebrafish. Growth rates of WT and acvr2a −/− b −/− were measured from juvenile stage to adult stage. In addition, effects of acvr2 on skeletal muscle were tested in histological, protein and molecular levels. As a result, acvr2a −/− b −/− exhibited a wider body trunk than WT and showed a significant increase in body weight and width from two months old. Histological analysis of skeletal muscle indicated that the size of muscle fiber in acvr2a −/− b −/− (female:1809 ± 123 μm 2 ; male: 2261 ± 130 μm 2 ) was larger than that in WT (709.8 ± 49 μm 2 ; 815 ± 53 μm 2 ). In addition, western blot of fast MyLc protein showed the protein synthesis of acvr2a −/− b −/− are increased. Besides, Histological analysis of heart showed the ventricle area is aslo increased in acvr2a −/− b −/− . Our results demonstrated acvr2 attends the development of muscle fiber and will cause muscle hypertrophy when they were knocked out in zebrafish. In conclusion, acvr2 in zebrafish can control the development of muscle fibers during posthatch growth.