Targeted myostatin loss-of-function mutation increases type II muscle fibers in Meishan pigs

Abstract

Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. The skeletal muscle in MSTN−/– mice is significantly hypertrophied, with muscle fiber type II increasing significantly while muscle fiber type I decreasing. However, it is still not clear how the skeletal muscle types change in MSTN−/– pigs, and how the mechanism for MSTN regulates fiber types, especially in large animals like pigs. This study conducted a comprehensive analysis of the composition of skeletal muscle fibers in MSTN−/– pigs produced in our laboratory. It was observed that, compared with wild-type (WT) pigs, both the total mass of skeletal muscle and type IIb muscle fibers increased significantly (P<0.01), while the type I and type IIa muscle fibers decreased significantly (P<0.01), in MSTN−/– Meishan pigs. In addition, to explore the influence of MSTN on muscle fiber type and its regulation mechanism in the embryonic stage, this study selected a few genes (Myf5, Mef2d, MyoD and Six1) associated with muscle fiber type and validated their expression by quantitative RT-PCR. Herein, it was found that Myh7, Myh2, Myh4 and Myh1 can be detected in the skeletal muscle of pigs at 65 days of gestation (dg). Compared with WT pigs, in MSTN−/– Meishan pigs, Myh7 decreased significantly (P<0.01), while Myh4 (P<0.001) and Myh1 (P<0.05) increased significantly. Meanwhile, the increased expression of Myf5 (P<0.05), Mef2d (P<0.01) and Six1 (P<0.05) in MSTN−/– Meishan pigs suggested that MSTN should regulate the directional development of muscle fiber types in the early stage of embryonic development. Thus, at the embryonic stage, the type II muscle fibers began to increase in MSTN−/– pigs. These results can provide valuable information not only for pig meat quality improvement, but also for the study of human skeletal muscle development and disease treatment.