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
ISSN1422-0067
卷号17期号:10
发表状态已发表
DOI10.3390/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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