title: CRISPR/Cas9-mediated GJA8 knockout in rabbits recapitulates human congenital cataracts.
abstract: Cataracts are the leading cause of vision loss in the world, although surgical treatment can restore vision in cataract patients. Until now, there have been no adequate animal models for in vivo studies of artificial lens safety and drug interactions. Genetic studies have demonstrated that GJA8 is involved in maintaining lens opacity and proper lens development. In this study, a cataract model with GJA8 gene knockout was developed via co-injection of Cas9/sgRNA mRNA into rabbit zygotes. Our results showed that gene mutation efficiency in the GJA8 locus reached 98.7% in embryos and 100% in pups, demonstrating that the Cas9/sgRNA system is a highly efficient tool for gene editing in rabbits. In agreement with other studies, our genetic and histology results showed that impaired GJA8 function caused microphthalmia, small lens size and cataracts. In summary, our novel rabbit model of cataracts will be an important drug-screening tool for cataract prevention and treatment.
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Sui
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Chen
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.
authors.forename: Jichao
authors.initials: J
authors.lastname: Deng
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.|College of Life and Health Sciences, Northeastern University, Shen Yang, China.
authors.forename: Yongye
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Song
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, Changchun, 130062, China.|Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Liangxue
authors.initials: L
authors.lastname: Lai
mesh_terms: D000818:Animals; D001483:Base Sequence; D064113:CRISPR-Cas Systems; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D017630:Connexins / Q000235:genetics*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D018390:Gene Targeting; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D010641:Phenotype; D011817:Rabbits; D015053:Zygote / Q000378:metabolism; D000099264:Connexin 50
chemical_list: D017630:Connexins; D000099264:Connexin 50