Müller M, Brenig B, Winnacker E L, Brem G
Institut für Molekulare Tierzucht, Ludwig-Maximilians-Universität München, Germany.
Gene. 1992 Nov 16;121(2):263-70. doi: 10.1016/0378-1119(92)90130-h.
An important aspect of gene transfer into farm animals is the improvement of disease resistance. The mouse Mx1 protein is known to be sufficient to confer resistance to influenza viruses. Gene constructs containing the mouse Mx1 cDNA controlled by the human metallothionein IIA promoter (hMTIIA::Mx), the SV40 early enhancer/promoter region (SV40::Mx) and the mouse Mx1 promoter (mMx::Mx) were transferred into pigs. The results of the gene transfer experiments with the hMTIIA::Mx and the SV40::Mx constructs indicate that the permanent high-level synthesis of Mx1 might be deleterious to the organism: the gene transfer efficiency was surprisingly low, and all transgenic piglets born had rearrangements in their transgene copies that abolished protein synthesis. The use of the interferon (IFN)- and virus-inducible mMx::Mx construct resulted in normal gene transfer efficiency. Two transgenic pig lines could be established which expressed IFN-inducible mouse Mx1 mRNA. Extensive protein analysis did not detect mouse Mx1 in IFN-treated transgenic animals.
将基因导入农场动物的一个重要方面是提高抗病能力。已知小鼠Mx1蛋白足以赋予对流感病毒的抗性。含有由人金属硫蛋白IIA启动子（hMTIIA::Mx）、SV40早期增强子/启动子区域（SV40::Mx）和小鼠Mx1启动子（mMx::Mx）控制的小鼠Mx1 cDNA的基因构建体被导入猪体内。用hMTIIA::Mx和SV40::Mx构建体进行的基因转移实验结果表明，Mx1的永久性高水平合成可能对生物体有害：基因转移效率出奇地低，所有出生的转基因仔猪的转基因拷贝都发生了重排，从而消除了蛋白质合成。使用干扰素（IFN）和病毒诱导的mMx::Mx构建体导致正常的基因转移效率。可以建立两个表达IFN诱导的小鼠Mx1 mRNA的转基因猪系。广泛的蛋白质分析在经IFN处理的转基因动物中未检测到小鼠Mx1。
