title: Generation and evaluation of Myostatin knock-out rabbits and goats using CRISPR/Cas9 system.
abstract: Myostatin (Mstn) is a conserved negative regulator of skeletal muscle mass in mammals. However, whether precise disruption of Mstn in livestock can be achieved and safely used to improve meat productivity has not been proven. We applied CRISPR/Cas9 system to generate Mstn knock-out (KO) rabbits and goats and then analyzed the changes in their phenotypes to answer this question. We efficiently generated 24 Mstn KO rabbits out of 32 newborn infants after embryo injection with two sgRNAs targeting rabbit Mstn, and found that the Mstn KO rabbits exhibited increased birthweight and a significantly increase in the weight ratios of the quadriceps and biceps muscles to the whole body. Mstn KO also caused high probability of enlarged tongue phenomenon and severe health problems such as stillbirth and early stage death. Using the same method, one out of four goats was generated with edition at Mstn locus. The early stage growth rate of this goat outperformed the control goats. In conclusion, we efficiently generated Mstn KO rabbits and goats using CRISPR/Cas9 technology. However, Mstn KO causes severe health problems and may also have the same effects on other species. This safety issue must be studied further before applied to animal reproduction processes.
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Rihong
authors.initials: R
authors.lastname: Guo
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Akeagen, Irvine, CA 92614, USA.
authors.forename: Libin
authors.initials: L
authors.lastname: Cui
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Mingtian
authors.initials: M
authors.lastname: Deng
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Guomin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Ruoxin
authors.initials: R
authors.lastname: Jia
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Kaiping
authors.initials: K
authors.lastname: Deng
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Mingrui
authors.initials: M
authors.lastname: Huang
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics* / Q000254:growth & development; D064113:CRISPR-Cas Systems / Q000235:genetics*; D055786:Gene Knockout Techniques; D006041:Goats / Q000235:genetics; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D055435:Myostatin / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011817:Rabbits
chemical_list: D055435:Myostatin