title: Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs.
abstract: 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.
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.|State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Qian
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.
authors.forename: Maoxue
authors.initials: M
authors.lastname: Tang
authors.affiliation: Dept of Human Nutrition, Food and Animal Sciences, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA.
authors.forename: Jinzeng
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.|State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, P.R. China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Cai
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.
authors.forename: Shengwang
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.|Institute of Animal Sciences, Qingdao, 266100, P.R. China.
authors.forename: Hegang
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Animal Sciences, Qingdao, 266100, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Gao
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.
authors.forename: Dezun
authors.initials: D
authors.lastname: Ma
authors.affiliation: College of Animal Medicine, China Agricultural University, Beijing, 100193, P.R. China.
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, P.R. China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: An
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.
authors.forename: Kui
authors.initials: K
authors.lastname: Li
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Cui
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004720:Endonucleases / Q000378:metabolism*; D063427:Food Quality; D015870:Gene Expression; D055786:Gene Knockout Techniques; D018390:Gene Targeting / Q000379:methods; D056726:Genetic Association Studies; D005838:Genotype; D006984:Hypertrophy; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000069466:Red Meat / Q000592:standards; D013552:Swine; D016335:Zinc Fingers
chemical_list: D055435:Myostatin; D012333:RNA, Messenger; D004720:Endonucleases