Establishment of severe combined immune deficient mice introduced with human MDR1 geneinducted by murine endothelin promoter

人胶质瘤通常由于血脑屏障（BBB）的存在而表现出内在的多药耐药，其中由人多药耐药基因MDR1编码的膜相关p -糖蛋白（PGp）发挥了一定的作用。我们建立了具有小鼠内皮素驱动的人MDR1基因的严重联合免疫缺陷（SCID）小鼠。然后，我们正在研究皮下移植的人类胶质瘤对长春新碱（VCR）、阿霉素（DOX）和尼莫司汀（ACNU）的药物敏感性。我们通过逆转录聚合酶链反应检测了MDR1基因在异种移植物中的表达水平，并通过免疫组织化学检测了PGp的定位。免疫组化结果显示，PGp仅局限于异种移植物的基质血管。正在进行的体内化学敏感性试验将为我们提供一些关于PGp在基质血管上表达作为人类胶质瘤多药耐药的主要因素的见解。

Human glioma usually shows intrinsic multidrug resistance due to the blood brain barrier (BBB), in which membrane-associated P-glycoprotein (PGp) encoded by human multidrug resistance gene MDR1 plays certain roles. We established severe combined immune deficient (SCID) mice harboring murine endothelin driven human MDR1 gene. Then, we are studying drug sensitivity to vincristine (VCR), doxorubicin (DOX) and nimustine (ACNU) in subcutaneously xenotransplanted human glioma. We examined the levels of MDR1 gene expression in the xenografts by reverse transcriptase-polymerase chain reaction, and the localization of PGp by immunohistochemistry. The localization of PGp was limited to the stromal vessels in the xenografts by immunohistochemistry. The in vivo chemosensitivity test, now going, will provide us some insights for PGp expressed on the stromal vessels as a major contributing factor to multidrug resistance in human glioma.