NDLI: Transgenic expression of human cytoxic T-lymphocyte associated antigen4-Immunoglobulin (hCTLA4Ig) by porcine skin for xenogeneic skin grafting

Content Provider	Springer Nature Link
Author	Wang, Yong Yang, Hua Qiang Jiang, Wen Fan, Na Na Zhao, Ben Tian Ou Yang, Zhen Liu, Zhao Ming Zhao, Yu Yang, Dong Shan Zhou, Xiao Yang Shang, Hai Tao Wang, Lu Lu Xiang, Peng Ying Ge, Liang Peng Wei, Hong Lai, Liang Xue
Copyright Year	2014
Abstract	Porcine skin is frequently used as a substitute of human skin to cover large wounds in clinic practice of wound care. In our previous work, we found that transgenic expression of human cytoxicT-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) in murine skin graft remarkably prolonged its survival in xenogeneic wounds without extensive immunosuppression in recipients, suggesting that transgenic hCTLA4Ig expression in skin graft may be an effective and safe method to prolong xenogeneic skin graft survival. In this work, using a transgene construct containing hCTLA4Ig coding sequence under the drive of human Keratine 14 (k14) promoter, hCTLA4Ig transgenic pigs were generated by somatic nuclear transfer. The derived transgenic pigs were healthy and exhibited no signs of susceptibility to infection. The hCTLA4Ig transgene was stably transmitted through germline over generations, and thereby a transgenic pig colony was established. In the derived transgenic pigs, hCTLA4Ig expression in skin was shown to be genetically stable over generations, and detected in heart, kidney and corneal as well as in skin. Transgenic hCTLA4Ig protein in pigs exhibited expected biological activity as it suppressed human lymphocyte proliferation in human mixed lymphocyte culture to extents comparable to those of commercially purchased purified hCTLA4Ig protein. In skin grafting from pigs to rats, transgenic porcine skin grafts exhibited remarkably prolonged survival compared to the wild-type skin grafts derived from the same pig strain (13.33 ± 3.64 vs. 6.25 ± 2.49 days, P < 0.01), further indicating that the transgenic hCTLA4Ig protein was biologically active and capable of extending porcine skin graft survival in xenogeneic wounds. The transgenic pigs generated in this work can be used as a reproducible resource to provide porcine skin grafts with extended survival for wound coverage, and also as donors to investigate the impacts of hCTLA4Ig on xenotransplantation of other organs (heart, kidney and corneal) due to the ectopic transgenic hCTLA4Ig expression.
Starting Page	199
Ending Page	211
Page Count	13
File Format	PDF
ISSN	09628819
Journal	Transgenic Research
Volume Number	24
Issue Number	2
e-ISSN	15739368
Language	English
Publisher	Springer International Publishing
Publisher Date	2014-09-19
Publisher Place	Cham
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	hCTLA4Ig Transgenic pigs Skin grafting Xenotransplantation Molecular Medicine Plant Genetics & Genomics Animal Genetics and Genomics Plant Sciences Transgenics
Content Type	Text
Resource Type	Article
Subject	Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science

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