NDLI: Generation of α-1,3-galactosyltransferase knocked-out transgenic cloned pigs with knocked-in five human genes

Content Provider	Springer Nature Link
Author	Kwon, Dae Jin Kim, Dong Hwan Hwang, In Sul Kim, Dong Ern Kim, Hyung Joo Kim, Jang Seong Lee, Kichoon Im, Gi Sun Lee, Jeong Woong Hwang, Seongsoo
Copyright Year	2016
Abstract	Recent progress in genetic manipulation of pigs designated for xenotransplantation ha6s shown considerable promise on xenograft survival in primates. However, genetic modification of multiple genes in donor pigs by knock-out and knock-in technologies, aiming to enhance immunological tolerance against transplanted organs in the recipients, has not been evaluated for health issues of donor pigs. We produced transgenic Massachusetts General Hospital piglets by knocking-out the α-1,3-galactosyltransferase (GT) gene and by simultaneously knocking-in an expression cassette containing five different human genes including, DAF, CD39, TFPI, C1 inhibitor (C1-INH), and TNFAIP3 (A20) [GT$^{−(DAF/CD39/TFPI/C1-INH/TNFAIP3)/+}$] that are connected by 2A peptide cleavage sequences to release individual proteins from a single translational product. All five individual protein products were successfully produced as determined by western blotting of umbilical cords from the newborn transgenic pigs. Although gross observation and histological examination revealed no significant pathological abnormality in transgenic piglets, hematological examination found that the transgenic piglets had abnormally low numbers of platelets and WBCs, including neutrophils, eosinophils, basophils, and lymphocytes. However, transgenic piglets had similar numbers of RBC and values of parameters related to RBC compared to the control littermate piglets. These data suggest that transgenic expression of those human genes in pigs impaired hematopoiesis except for erythropoiesis. In conclusion, our data suggest that transgenic expression of up to five different genes can be efficiently achieved and provide the basis for determining optimal dosages of transgene expression and combinations of the transgenes to warrant production of transgenic donor pigs without health issues.
Starting Page	153
Ending Page	163
Page Count	11
File Format	PDF
ISSN	09628819
Journal	Transgenic Research
Volume Number	26
Issue Number	1
e-ISSN	15739368
Language	English
Publisher	Springer International Publishing
Publisher Date	2016-08-23
Publisher Place	Cham
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Multi-transgenic pigs Xenotransplantation Immune rejection Leucopenia Thrombocytopenia Animal Genetics and Genomics Plant Genetics & Genomics Transgenics Biomedical Engineering/Biotechnology Genetic Engineering Molecular Medicine
Content Type	Text
Resource Type	Article
Subject	Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science

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