半乳糖-α1,3-半乳糖表位敲除及人膜辅因子蛋白hCD46猪中衰老相关基因的稳定调控

Stable Regulation of Senescence-Related Genes in Galactose-alpha1,3-galactose Epitope Knockout and Human Membrane Cofactor Protein hCD46 Pig.

作者信息

Ullah Imran, Lee Ran, Oh Keon Bong, Kim Youngim, Woo Jae-Seok, Hwang Seongsoo, Im Gi-Sun, Ock Sun A

机构信息

Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea.

出版信息

Transplant Proc. 2019 Jul-Aug;51(6):2043-2050. doi: 10.1016/j.transproceed.2019.03.028.

DOI:10.1016/j.transproceed.2019.03.028

PMID:31399182

Abstract

BACKGROUND

Pigs are considered suitable animal donor models for xenotransplantation. For successful organ transplantation, immune rejection must be overcome. Xenotransplantation has recently been successfully performed using galactose-alpha1,3-galactose epitopes knockout (GalTKO) and a human membrane cofactor protein (hCD46) in a pig model. However, the growth and lifespan of the grafted organ have not been evaluated. Therefore, in the present study we evaluated aging and 84 senescence-related genes using the RT Profiler PCR array and whole blood samples from GalTKO/hCD46 Massachusetts General Hospital (MGH) pigs.

METHODS

Experimental groups were double GalTKO/hCD46 (5-month-old), single GalTKO/hCD46 (2-year-old), and non-genetically modified (>3.5-year-old; control group within the same strain). Age-matched white hairless Yucatan (WHY) miniature pig groups were used as controls.

RESULTS

Among the 19 senescence-related genes selected from the 84 genes for further evaluation, 13 were upregulated in the double GalTKO/hCD46 MGH pigs compared to control MGH pigs; however, in WHY pigs, only 4 genes were up- or down-regulated among the 19 genes. Moreover, in double GalTKO/hCD46 MGH and WHY pigs, the expression of the 19 genes changed only 1- to 2-fold, suggesting that there were no significant differences in senescence signals between the 2 pig lines.

CONCLUSIONS

The present results indicate that the double GalTKO/hCD46 MGH pig might be a suitable model for human xenotransplantation studies. However, we used a limited number of experimental individuals, so further studies using larger experimental groups should be conducted to verify the present results.

摘要

背景

猪被认为是异种移植合适的动物供体模型。为了成功进行器官移植，必须克服免疫排斥。最近在猪模型中使用α1,3-半乳糖表位敲除（GalTKO）和人膜辅因子蛋白（hCD46）成功进行了异种移植。然而，移植器官的生长和寿命尚未得到评估。因此，在本研究中，我们使用RT Profiler PCR芯片和来自GalTKO/hCD46麻省总医院（MGH）猪的全血样本评估了衰老和84个衰老相关基因。

方法

实验组为双GalTKO/hCD46（5月龄）、单GalTKO/hCD46（2岁）和非转基因（>3.5岁；同一品系内的对照组）。年龄匹配的白色无毛尤卡坦（WHY）小型猪组用作对照。

结果

在从84个基因中选出的19个用于进一步评估的衰老相关基因中，与对照MGH猪相比，双GalTKO/hCD46 MGH猪中有13个基因上调；然而，在WHY猪中，这19个基因中只有4个基因上调或下调。此外，在双GalTKO/hCD46 MGH猪和WHY猪中，19个基因的表达仅变化1至2倍，表明这两个猪系之间的衰老信号没有显著差异。