Generation by somatic cell nuclear transfer of GGTA1 knockout pigs expressing soluble human TNFRI-Fc and human HO-1

Geon A. Kim, Eun Mi Lee, Bumrae Cho, Zahid Alam, Su Jin Kim, Sanghoon Lee, Hyun Ju Oh, Jong-Ik Hwang, Curie Ahn, Byeong Chun Lee

Research output: Contribution to journalArticle

Abstract

Herein, we successfully generated transgenic pigs expressing both soluble human tumor necrosis factor receptor I IgG 1 -Fc (shTNFRI-Fc) and human hemagglutinin (HA)-tagged-human heme oxygenase-1 (hHO-1) without Gal epitope. Healthy cloned pigs were produced by somatic cell nuclear transfer (SCNT) using the genetically modified cells. The genetic disruption of the GGTA1 genes and absence of expression of BS-IB4 lectin in tail-derived fibroblast of the SCNT-generated piglets were successfully confirmed. The expression of shTNFRI-Fc and HAhHO-1 was fully identified with protective effect against oxidative stress and apoptosis stimulation. Antibody-mediated complement-dependent cytotoxicity assay for examining the immuno-reactivity of transgenically derived pig cells showed that pigs lacking GGTA1 with the expression of double genes reduce the humoral barrier to xenotransplantation, more than pigs simply expressing double genes and the wild type. Through this approach, rapid production of a pig strain deficient in various genes may be expected to be applicable for xenotransplantation research without extensive breeding protocols.

Original languageEnglish
Pages (from-to)91-102
Number of pages12
JournalTransgenic Research
Volume28
Issue number1
DOIs
Publication statusPublished - 2019 Feb 1

Fingerprint

somatic cells
Swine
swine
xenotransplantation
tumor necrosis factors
Heterologous Transplantation
Tumor Necrosis Factor Receptors
heme oxygenase (biliverdin-producing)
Immunoglobulin G
receptors
genes
Gene Expression
gene targeting
hemagglutinins
Heme Oxygenase-1
lectins
epitopes
fibroblasts
protective effect
cytotoxicity

Keywords

  • Alpha1,3-galactosyltransferase gene
  • Genetically engineered pigs
  • Soluble human TNFRI-Fc and human HO-1
  • Somatic cell nuclear transfer
  • Xenotransplantation

ASJC Scopus subject areas

  • Biotechnology
  • Animal Science and Zoology
  • Genetics
  • Agronomy and Crop Science

Cite this

Generation by somatic cell nuclear transfer of GGTA1 knockout pigs expressing soluble human TNFRI-Fc and human HO-1. / Kim, Geon A.; Lee, Eun Mi; Cho, Bumrae; Alam, Zahid; Kim, Su Jin; Lee, Sanghoon; Oh, Hyun Ju; Hwang, Jong-Ik; Ahn, Curie; Lee, Byeong Chun.

In: Transgenic Research, Vol. 28, No. 1, 01.02.2019, p. 91-102.

Research output: Contribution to journalArticle

Kim, Geon A. ; Lee, Eun Mi ; Cho, Bumrae ; Alam, Zahid ; Kim, Su Jin ; Lee, Sanghoon ; Oh, Hyun Ju ; Hwang, Jong-Ik ; Ahn, Curie ; Lee, Byeong Chun. / Generation by somatic cell nuclear transfer of GGTA1 knockout pigs expressing soluble human TNFRI-Fc and human HO-1. In: Transgenic Research. 2019 ; Vol. 28, No. 1. pp. 91-102.
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