Frameshift mutation in myostatin gene by zinc-finger nucleases results in a significant increase in muscle mass in Meishan sows

Abstract

Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. A significant increase in skeletal muscle was observed in Mstn −/− mice compared with wild-type mice. So far, there has been no report on porcine MSTN mutations leading to skeletal muscle hypertrophy. In this report a MSTN frameshift mutation missing 11 nucleotides in exon 2 was introduced into Meishan pigs by zinc finger nuclease (ZFN) technology. ZFN-edited MSTN −/− Meishan pigs were successfully produced by a cloning method of somatic cell nucleus transfer. Results from slaughter experiments indicated that lean meat yield increased 16.53% in about 80 kg (10-months-old) MSTN −/− Meishan sows compared with their corresponding wild-type counterparts. The lean percentage of carcass from MSTN −/− sows was 61.20% vs 48.25% for MSTN +/− sows and 44.67% for wild-type sows. The fat of MSTN −/− sows was significantly lower than that of MSTN +/− and wild-type sows. The loin eye area of MSTN −/− Meishan sows (56.42 cm 2) was greater than that of MSTN +/− (37.39 cm 2) and wild-type (26.26 cm 2) sows. The muscle fibre area of longissimus muscle in wild-type Meishan sows (1 946 μm 2) was significantly greater than that of MSTN +/− (1 324 μm 2) and MSTN − /− (1 419 μm 2) sows. Moreover the significantly increased skeletal muscle in these MSTN −/− Meishan sows was mainly due to the increase in the number of myofibres rather than to hypertrophy. Compared with wild-type Meishan sows, it was noted that myofibres had transformed from type I to IIB in MSTN −/− Meishan sows. Our present study demonstrated that frameshift mutation in MSTN by ZFN technology led to a significant increase in muscle mass and a significant decrease in fat content in Meishan sows.