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Postneonatal Mortality and Liver Changes in Cloned Pigs Associated with Human Tumor Necrosis Factor Receptor I-Fc and Human Heme Oxygenase-1 Overexpression

Authors
Kim, Geon A.Jin, Jun-XueLee, SanghoonTaweechaipaisankul, AnukulOh, Hyun JuHwang, Joing-IkAhn, CurieSaadeldin, Islam M.Lee, Byeong Chun
Issue Date
2017
Publisher
HINDAWI LTD
Citation
BIOMED RESEARCH INTERNATIONAL, v.2017
Indexed
SCIE
SCOPUS
Journal Title
BIOMED RESEARCH INTERNATIONAL
Volume
2017
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/132427
DOI
10.1155/2017/5276576
ISSN
2314-6133
Abstract
Soluble human tumor necrosis factor (shTNFRI-Fc) and human heme oxygenase 1 (hHO-1) are key regulators for protection against oxidative and inflammatory injury for xenotransplantation. Somatic cells with more than 10 copy numbers of shTNFRI-Fc and hHO-1 were employed in somatic cell nuclear transfer to generate cloned pigs, thereby resulting in seven cloned piglets. However, produced piglets were all dead within 24 hours after birth. Obviously, postnatal death with liver apoptosis was reported in the higher copy number of shTNFRI-Fc and hHO-1 piglets. In liver, the transcript levels of ferritin heavy chain, light chain, transferrin, and inducible nitric oxide synthase were significantly highly expressed compared to those of lower copy number of shTNFRI-Fc and hHO-1 piglets (P < 0.05). Also, H2O2 contents were increased, and superoxide dismutase was significantly lower in the higher copy number of shTNFRI-Fc and hHO-1 piglets (P < 0.05). These results indicate that TNFRI-Fc and hHO-1 overexpression may apparently induce free iron in the liver and exert oxidative stress by enhancing reactive oxygen species production and block normal postneonatal liver metabolism.
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