携带小片段红系特异增强子的人β-珠蛋白基因在小鼠体内表达的研究  

Expression of Human β-globin Gene after Retroviral Mediated Gene Transfer into Murine Hematopoietic Stem Cells

作　　者：翟锦彬 刘德培 王晶[2] 陈迪 郑勇 梁植权[2] 

机构地区：[1]中国医学院科学基础医学研究所,北京100005 [2]中国协和医科大学基础医学院医学分子生物学国家重点实验室,北京100005

出　　处：《高技术通讯》1999年第11期7-10,共4页Chinese High Technology Letters

基　　金：863计划资助项目

摘　　要：采用回体（ｅｘ ｖｉｖｏ） 基因转移策略， 分析了人β－珠蛋白基因在小鼠体内的整合和表达。研究发现， 在小鼠ＣＦＵ－Ｓ１２中检测到转移的人β－珠蛋白基因的整合， 其表达水平约为内源性鼠α－珠蛋白基因的０．５％ ～５％ 。在两只长期造血重建小鼠的骨髓、脾及胸腺和另一只小鼠的骨髓及脾中整合有人β－珠蛋白基因， 人β－珠蛋白基因在一只重建小鼠的骨髓和脾中表达，表达水平约为鼠内源α－珠蛋白基因的７％ ，表明反转录病毒载体介导的人β－珠蛋白基因可稳定整合在小鼠骨髓造血干细胞中，To examine the in vivo properties of retroviral recombinant carrying partially deleted human β globin gene(Δβ) and truncated erythroid enhancer (342 bp of 5HS2) at the mRNA levels following short and long term reconstitution in mice with infected marrow cells, the human β globin gene was transferred into murine hematopoietic progenitor cells and the integration and expression of transferred gene were analyzed by soughern blot and RNase protection assay or RT PCR. Results showed that the transferred human β globin gene was detected in murine CFU S 12 and the expression level was about 0.5%～5% of the endogenous mouse α globin gene. In mice surviving long term transplanted with bone marrow cells transduced with high titer virus, bone marrow, spleen and thymus from two mice and bone marrow and spleen from another mouse contained the intact proviral genome. Long term expression of the transferred gene was seen in one mouse at the level of 7% of endogenous murine α globin gene.

关 键 词：Β-珠蛋白基因 Β-地中海贫血 基因治疗 

分 类 号：R556[医药卫生—血液循环系统疾病] Q753[医药卫生—内科学]