Frontiers in Immunology (Aug 2022)
Development of RAG2-/-IL2Rγ-/Y immune deficient FAH-knockout miniature pig
- Heng Zhao,
- Heng Zhao,
- Heng Zhao,
- Weijian Ye,
- Weijian Ye,
- Jianxiong Guo,
- Jianxiong Guo,
- Jiaoxiang Wang,
- Jiaoxiang Wang,
- Jiaoxiang Wang,
- Deling Jiao,
- Deling Jiao,
- Deling Jiao,
- Kaixiang Xu,
- Kaixiang Xu,
- Kaixiang Xu,
- Chang Yang,
- Chang Yang,
- Shuhan Chen,
- Shuhan Chen,
- Shuhan Chen,
- Muhammad Ameen Jamal,
- Zhongbin Bai,
- Taiyun Wei,
- Taiyun Wei,
- Jie Cai,
- Jie Cai,
- Tien Dat Nguyen,
- Tien Dat Nguyen,
- Tien Dat Nguyen,
- Yubo Qing,
- Yubo Qing,
- Yubo Qing,
- Wenmin Cheng,
- Wenmin Cheng,
- Wenmin Cheng,
- Baoyu Jia,
- Baoyu Jia,
- Baoyu Jia,
- Honghui Li,
- Honghui Li,
- Honghui Li,
- Hong-Ye Zhao,
- Hong-Ye Zhao,
- Qingfeng Chen,
- Qingfeng Chen,
- Hong-Jiang Wei,
- Hong-Jiang Wei,
- Hong-Jiang Wei,
- Hong-Jiang Wei
Affiliations
- Heng Zhao
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Heng Zhao
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Heng Zhao
- College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
- Weijian Ye
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore
- Weijian Ye
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Jianxiong Guo
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Jianxiong Guo
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Jiaoxiang Wang
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Jiaoxiang Wang
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Jiaoxiang Wang
- College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
- Deling Jiao
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Deling Jiao
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Deling Jiao
- Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, China
- Kaixiang Xu
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Kaixiang Xu
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Kaixiang Xu
- Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, China
- Chang Yang
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Chang Yang
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Shuhan Chen
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Shuhan Chen
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Shuhan Chen
- College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
- Muhammad Ameen Jamal
- Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
- Zhongbin Bai
- College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
- Taiyun Wei
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Taiyun Wei
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Jie Cai
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Jie Cai
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Tien Dat Nguyen
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Tien Dat Nguyen
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Tien Dat Nguyen
- Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, China
- Yubo Qing
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Yubo Qing
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Yubo Qing
- College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
- Wenmin Cheng
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Wenmin Cheng
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Wenmin Cheng
- Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, China
- Baoyu Jia
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Baoyu Jia
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Baoyu Jia
- College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
- Honghui Li
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Honghui Li
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Honghui Li
- Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, China
- Hong-Ye Zhao
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Hong-Ye Zhao
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Qingfeng Chen
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore
- Qingfeng Chen
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Hong-Jiang Wei
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming, China
- Hong-Jiang Wei
- Yunnan Province Xenotransplantation Research Engineering Centre, Yunnan Agricultural University, Kunming, China
- Hong-Jiang Wei
- College of Veterinary Medicine, Yunnan Agricultural University, Kunming, China
- Hong-Jiang Wei
- Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
- DOI
- https://doi.org/10.3389/fimmu.2022.950194
- Journal volume & issue
-
Vol. 13
Abstract
Human hepatocyte transplantation for liver disease treatment have been hampered by the lack of quality human hepatocytes. Pigs with their large body size, longevity and physiological similarities with human are appropriate animal models for the in vivo expansion of human hepatocytes. Here we report on the generation of RAG2-/-IL2Rγ-/YFAH-/- (RGFKO) pigs via CRISPR/Cas9 system and somatic cell nuclear transfer. We showed that thymic and splenic development in RGFKO pigs was impaired. V(D)J recombination processes were also inactivated. Consequently, RGFKO pigs had significantly reduced numbers of porcine T, B and NK cells. Moreover, due to the loss of FAH, porcine hepatocytes continuously undergo apoptosis and consequently suffer hepatic damage. Thus, RGFKO pigs are both immune deficient and constantly suffer liver injury in the absence of NTBC supplementation. These results suggest that RGFKO pigs have the potential to be engrafted with human hepatocytes without immune rejection, thereby allowing for large scale expansion of human hepatocytes.
Keywords
