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Disabling of nephrogenesis in porcine embryos via CRISPR/Cas9-mediated SIX1 and SIX4 gene targeting.
Wang, Junzheng; Liu, Manling; Zhao, Lihua; Li, Yanru; Zhang, Manling; Jin, Yong; Xiong, Qiang; Liu, Xiaorui; Zhang, Lining; Jiang, Haibin; Chen, Qiaoyu; Wang, Chenyu; You, Zhihuan; Yang, Haiyuan; Cao, Changchun; Dai, Yifan; Li, Rongfeng.
Afiliação
  • Wang J; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Liu M; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Zhao L; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Li Y; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Zhang M; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
  • Jin Y; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Xiong Q; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China.
  • Liu X; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Zhang L; Department of Nephrology, The Affiliated Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
  • Jiang H; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Chen Q; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Wang C; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • You Z; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Yang H; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Cao C; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Dai Y; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
  • Li R; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
Xenotransplantation ; 26(3): e12484, 2019 05.
Article em En | MEDLINE | ID: mdl-30623494
ABSTRACT
SIX1 and SIX4 genes play critical roles in kidney development. We evaluated the effect of these genes on pig kidney development by generating SIX1-/- and SIX1-/- /SIX4-/- pig foetuses using CRISPR/Cas9 and somatic cell nuclear transfer. We obtained 3 SIX1-/- foetuses and 16 SIX1-/- /SIX4-/- foetuses at different developmental stages. The SIX1-/- foetuses showed a migration block of the left kidney and a smaller size for both kidneys. The ureteric bud failed to form the normal branching and collecting system. Abnormal expressions of kidney development-related genes (downregulation of PAX2, PAX8, and BMP4 and upregulation of EYA1 and SALL1) were also observed in SIX1-/- foetal kidneys and confirmed in vitro in porcine kidney epithelial cells (PK15) following SIX1 gene deletion. The SIX1-/- /SIX4-/- foetuses exhibited more severe phenotypes, with most foetuses showing retarded development at early stages of gestation. The kidney developed only to the initial stage of metanephros formation. These results demonstrated that SIX1 and SIX4 are key genes for porcine metanephros development. The creation of kidney-deficient porcine foetuses provides a platform for generating human kidneys inside pigs using blastocyst complementation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Genes Homeobox / Marcação de Genes / Sistemas CRISPR-Cas Limite: Animals Idioma: En Revista: Xenotransplantation Assunto da revista: TRANSPLANTE Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Genes Homeobox / Marcação de Genes / Sistemas CRISPR-Cas Limite: Animals Idioma: En Revista: Xenotransplantation Assunto da revista: TRANSPLANTE Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China