【摘要】 肌肉生长抑制素(myostatin, MSTN)是肌肉发育的重要负向调控因子。自然界中多个物种的MSTN突变会产生肌肉肥大的性状,但在猪(Sus scrofa)中还未发现MSTN的自然突变。中国农业科学院北京畜牧兽医研究所利用锌指核酶(zinc-finger nucleases, ZFN)编辑技术敲除梅山猪胎儿成纤维细胞的MSTN基因,并结合体细胞核移植(somatic cell nuclear transplantation)及胚胎移植(embryo transplantation)技术获得了国际首例MSTN基因编辑克隆梅山猪。该品系的纯合子MSTN (MSTN-/-)编辑梅山猪具有明显的双肌性状,背部宽阔、臀部丰满、前肩发达,瘦肉率可达到60%以上,相比野生型(MSTN+/+)提高了近20%,达到了与外来猪种一样的瘦肉率水平,有效地解决了制约我国地方黑猪发展的技术瓶颈。该基因编辑猪的基因组内无任何标记基因、无脱靶现象及任何载体片段的整合,在动物健康及其产品安全方面更具有可靠性,并已被农业部批准进入生产性试验安全评价阶段,相关成果的制备专利和MSTN突变序列保护专利已经获得国家发明专利授权。目前该成果在安全性及其育种价值方面都具有很好的产业化前景,可为社会带来巨大的经济效益。更多还原

【Abstract】 Myostatin(MSTN) is an important negative regulator of muscle development. Mutations of MSTN gene can lead to muscle hypertrophy in many natural species. However, there was not been reported significant muscle phenotype in pigs(Sus scrofa) in association with MSTN mutation. Researchers from Institute of Animal Sciences, Chinese Academy of Agricultural Sciences used zinc-finger nucleases(ZFN)editing technique in combination with somatic cell nuclear transfer and embryo transfer techniques to knock out the MSTN gene of Meishan pig’s fetal fibroblast, and obtained the first MSTN gene editing Meishan pigs in the world. The homozygous MSTN mutation(MSTN-/-) Meishan pigs had a distinct double-muscle phenotype with broad back, full hips and well-developed front shoulders. The lean-meat rate could reach more than 60%,which was nearly 20% higher than wild type. It had reached the same level as exotic pig breeds, effectively solving the technical bottleneck that restricted the development of local black pigs in China. The gene editing pig had not any marker gene or any integrated carrier fragment in the genome, and there was no off-target phenomenon. It was more reliable in animal health and product safety. Additionally, it had been approved by the Ministry of Agriculture to enter the stage of production test safety evaluation. The patent for the preparation of the related achievements and the patent for the protection of MSTN mutant sequences had been granted by the National Invention Patents. At present, this achievement has good industrialization prospects in terms of safety and breeding value, which could bring enormous economic benefits to the society.更多还原