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Porcine Zygote Injection with Cas9/sgRNA Results in DMD-Modified Pig with Muscle Dystrophy | |
Yu, Hong-Hao1,2,3,4; Zhao, Heng2,3; Qing, Yu-Bo2,3; Pan, Wei-Rong3; Jia, Bao-Yu2,3; Zhao, Hong-Ye2; Huang, Xing-Xu1; Wei, Hong-Jiang2,3 | |
2016-10 | |
发表期刊 | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES |
ISSN | 1422-0067 |
卷号 | 17期号:10 |
发表状态 | 已发表 |
DOI | 10.3390/ijms17101668 |
摘要 | Dystrophinopathy, including Duchenne muscle dystrophy (DMD) and Becker muscle dystrophy (BMD) is an incurable X-linked hereditary muscle dystrophy caused by a mutation in the DMD gene in coding dystrophin. Advances in further understanding DMD/BMD for therapy are expected. Studies on mdx mice and dogs with muscle dystrophy provide limited insight into DMD disease mechanisms and therapeutic testing because of the different pathological manifestations. Miniature pigs share similar physiology and anatomy with humans and are thus an excellent animal model of human disease. Here, we successfully achieved precise DMD targeting in Chinese Diannan miniature pigs by co-injecting zygotes with Cas9 mRNA and sgRNA targeting DMD. Two piglets were obtained after embryo transfer, one of piglets was identified as DMD-modified individual via traditional cloning, sequencing and T7EN1 cleavage assay. An examination of targeting rates in the DMD-modified piglet revealed that sgRNA:Cas9-mediated on-target mosaic mutations were 70% and 60% of dystrophin alleles in skeletal and smooth muscle, respectively. Meanwhile, no detectable off-target mutations were found, highlighting the high specificity of genetic modification using CRISPR/Cas9. The DMD-modified piglet exhibited degenerative and disordered phenotypes in skeletal and cardiac muscle, and declining thickness of smooth muscle in the stomach and intestine. In conclusion, we successfully generated myopathy animal model by modifying the DMD via CRISPR/Cas9 system in a miniature pig. |
关键词 | CRISPR/Cas9 DMD pig disease model gene editing |
收录类别 | SCI |
语种 | 英语 |
资助项目 | naturalscience foundation key project of Yunnan province[2013FA016] |
WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
WOS类目 | Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary |
WOS记录号 | WOS:000387768300069 |
出版者 | MDPI |
WOS关键词 | DUCHENNE MUSCULAR-DYSTROPHY ; GENERATION ; HYPERTROPHY ; MODELS |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1682 |
专题 | 生命科学与技术学院_PI研究组_黄行许组 |
通讯作者 | Huang, Xing-Xu; Wei, Hong-Jiang |
作者单位 | 1.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 2.Yunnan Agr Univ, State Key Lab Conservat & Utilizat Bioresources Y, Kunming 650201, Peoples R China 3.Yunnan Agr Univ, Coll Anim Sci & Technol, Kunming 650201, Peoples R China 4.Yulin Univ, Res Ctr Life Sci, Yulin 719000, Peoples R China |
第一作者单位 | 生命科学与技术学院 |
通讯作者单位 | 生命科学与技术学院 |
第一作者的第一单位 | 生命科学与技术学院 |
推荐引用方式 GB/T 7714 | Yu, Hong-Hao,Zhao, Heng,Qing, Yu-Bo,et al. Porcine Zygote Injection with Cas9/sgRNA Results in DMD-Modified Pig with Muscle Dystrophy[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2016,17(10). |
APA | Yu, Hong-Hao.,Zhao, Heng.,Qing, Yu-Bo.,Pan, Wei-Rong.,Jia, Bao-Yu.,...&Wei, Hong-Jiang.(2016).Porcine Zygote Injection with Cas9/sgRNA Results in DMD-Modified Pig with Muscle Dystrophy.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,17(10). |
MLA | Yu, Hong-Hao,et al."Porcine Zygote Injection with Cas9/sgRNA Results in DMD-Modified Pig with Muscle Dystrophy".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 17.10(2016). |
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