Construction of a transgenic rat model, which is highly sensitive to HTLV-1 infection

人类T细胞白血病病毒1型（HTLV-1）在大鼠体内复制较差是由于大鼠细胞中Rex活性较低。人类CRM 1 （Rex的一个辅助因子）的大鼠同源性被发现是导致Rex活性低下的原因，因为它不支持对病毒RNA输出至关重要的Rex多聚合。在这个项目中，我们打算证明大鼠CRM1是htlv -1复制的主要阻断剂，并且在大鼠细胞中表达人CRM1足以恢复病毒蛋白的合成。最后，我们的目标是产生表达人类CRM1的转基因大鼠。然后我们得到了以下结果。1、成功建立表达人crm1的大鼠细胞系。2、在亲本大鼠细胞中，Rex活性处于检测不到的水平，而在人crm1转导的大鼠细胞中，Rex活性显著增强到与人细胞相似的水平。3、此外，人类CRMI的表达有效地恢复了HTLV-1产生病毒蛋白的能力。我们可以成功地培育出表达人类CRM1的转基因大鼠。

Human T cell leukemia virus type1 (HTLV-1) replicates poorly in rats owing to a low activity of Rex in rat cells. Rat autholog of human CRM 1, a cofactor of Rex, is found to be responsible for the poor activity of Rex, because it does not support the Rex multimerization, which is essential for viral RNA export. In this Project, we intended to demonstrate that rat CRM1 is a major block against HTLV-1replication and expression of human CRM1 in rat cells is sufficient to recover viral protein synthesis. Finally we aimed to produce a transgenic rat expressing human CRM1. Then we have gotten the following results.1, The human CRM1expressing rat cell lines were successfully established.2, In the parental rat cells, Rex activity was at undetectable level, while in the human CRM1-transduced rat cells, the Rex activity was significantly enhanced to the level similar to the human cells.3, Furthermore, the expression of human CRMI efficiently recovered the ability of HTLV-1 to produce viron proteins.4, We could successfully produce a transgenic rat expressing human CRM1.