Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs

• Published in: Scientific reports 2015-09, Vol.5 (1), p.14435-14435, Article 14435
• Main Authors: Qian, Lili, Tang, Maoxue, Yang, Jinzeng, Wang, Qingqing, Cai, Chunbo, Jiang, Shengwang, Li, Hegang, Jiang, Ke, Gao, Pengfei, Ma, Dezun, Chen, Yaoxing, An, Xiaorong, Li, Kui, Cui, Wentao
• Format: Article
• Language: English
• Subjects: 13/109; 42; 631/1647; 631/208; Animal models; Animals; Animals, Genetically Modified; Base Sequence; DNA Mutational Analysis; Endonucleases - metabolism; Food Quality; Gene Expression; Gene Knockout Techniques; Gene Targeting - methods; Genetic Association Studies; Genetic improvement; Genotype; Genotype & phenotype; Hogs; Humanities and Social Sciences; Hyperplasia; Hypertrophy; Indigenous animals; Meat; Meat production; MSTN gene; multidisciplinary; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Musculoskeletal system; Mutants; Mutation; Myostatin; Myostatin - genetics; Myostatin - metabolism; Nuclease; Organ Size; Phenotype; Red Meat - standards; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Skeletal muscle; Spine; Swine; Thorax; Vertebrae; Zinc finger proteins; Zinc Fingers
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep14435

Myostatin (MSTN) is a dominant inhibitor of skeletal muscle development and growth. Mutations in MSTN gene can lead to muscle hypertrophy or double-muscled (DM) phenotype in cattle, sheep, dog and human. However, there has not been reported significant muscle phenotypes in pigs in association with MSTN mutations. Pigs are an important source of meat production, as well as serve as a preferred animal model for the studies of human disease. To study the impacts of MSTN mutations on skeletal muscle growth in pigs, we generated MSTN -mutant Meishan pigs with no marker gene via zinc finger nucleases (ZFN) technology. The MSTN- mutant pigs developed and grew normally, had increased muscle mass with decreased fat accumulation compared with wild type pigs and homozygote MSTN mutant ( MSTN −/− ) pigs had apparent DM phenotype and individual muscle mass increased by 100% over their wild-type controls ( MSTN +/+ ) at eight months of age as a result of myofiber hyperplasia. Interestingly, 20% MSTN- mutant pigs had one extra thoracic vertebra. The MSTN- mutant pigs will not only offer a way of fast genetic improvement of lean meat for local fat-type indigenous pig breeds, but also serve as an important large animal model for biomedical studies of musculoskeletal formation, development and diseases.