Molecular Animal Breeding and Biotechnology, Department of Veterinary Sciences, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Munich, Germany.
Curr Opin Organ Transplant. 2010 Apr;15(2):201-6. doi: 10.1097/MOT.0b013e328336ba4a.
Appropriate expression of immunomodulatory and anticoagulant proteins on endothelial cells is essential to prevent rejection of vascularized porcine organs after transplantation into primates. Here, we review the promoter sequences used for the establishment of transgenic pigs, as organ donors for xenotransplantation.
Transgenic pigs were produced using viral, chicken, mouse, human, and porcine promoter sequences with ubiquitous or cell type-specific activity. In addition to the expression of human complement regulatory proteins, which were efficient to prevent hyperacute rejection of pig-to-primate xenografts, novel transgenes, targeting cellular rejection mechanisms, abnormal-blood coagulation, or the risk of viral transmission, have been published or announced in preliminary reports.
Accurate spatiotemporal expression of immunomodulatory and anticoagulant proteins on the endothelial cells of transgenic pigs is required for the successful xenotransplantation of vascularized organs into primates. Targeting transgene expression specifically to the cells critical for xenograft rejection may eliminate potential side effects of ubiquitous expression. Comparison of regulatory sequences from various species indicates that carefully selected porcine promoter sequences may be beneficial to achieve this aim.
在将血管化的猪器官移植到灵长类动物中后，内皮细胞上免疫调节和抗凝蛋白的适当表达对于防止排斥反应至关重要。在这里，我们回顾了用于建立转基因猪（作为异种移植供体的器官捐献者）的启动子序列。
使用具有普遍或细胞类型特异性活性的病毒、鸡、鼠、人、猪启动子序列，已经生产出了转基因猪。除了表达有效的人补体调节蛋白，可防止猪到灵长类动物异种移植物的超急性排斥反应外，还发表或初步报告了针对细胞排斥机制、异常凝血或病毒传播风险的新型转基因。
为了成功地将血管化器官异种移植到灵长类动物中，需要在转基因猪的内皮细胞上准确的时空表达免疫调节和抗凝蛋白。将转基因表达特异性靶向对异种移植物排斥至关重要的细胞，可能消除普遍表达的潜在副作用。来自不同物种的调控序列的比较表明，经过精心选择的猪启动子序列可能有助于实现这一目标。
