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.

Highlights

  • Implication of somatic cell nuclear transfer (SCNT) for the production of genetically modified pigs is widely accepted [1]

  • We focus on the function of shTNFRI-Fc and Heme oxygenase-1 (HO-1) in transgenic pigs to study the mechanism of shTNFRI-Fc and HO-1 on liver metabolism

  • Fibroblasts from white Yucatan pig (O-type blood) with ubiquitous expression of the shTNFRI-Fc and hHAHO-1 were used as donor cells for SCNT

Read more

Summary

Introduction

Implication of somatic cell nuclear transfer (SCNT) for the production of genetically modified pigs is widely accepted [1]. Since the first report for Gal deficiency pig production using SCNT [3], various transgenic pigs with multiple genes modifications including CD39, CD55, CD59, endothelial protein C receptor, and thrombomodulin were generated for xenotransplantation [4]. With this impressive success, the phenotype and characteristics of transgenic pigs for the practical use should be investigated. Transgene copy number can influence transgene expression in mouse [5] as well as in pigs [6]. Previous studies on transgenesis indicated that copy number of transgene could affect the clinical phenotype and mortality [7, 8]

Objectives
Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call