化学药物导致的与Friedreich共济失调相关的GAA重复序列不稳定性的研究  

Study on Chemotherapeutic Instability of the GAA Repeat Sequences Associated with Friedreich Ataxia

作　　者：赵宏宇[1,2] 蔡禄[1,2] 赵秀娟[1,2] 王晶妍[1,2] 陈元秀[1] 刘水峰[1] 

机构地区：[1]内蒙古科技大学数理与生物工程学院,包头014010 [2]内蒙古科技大学生物工程与技术研究所,包头014010

出　　处：《生物技术通报》2010年第1期147-152,共6页Biotechnology Bulletin

基　　金：国家自然科学基金项目(30460038);内蒙古自然科学基金重点项目(200508010102)

摘　　要：Friedreich共济失调是由位于FRDA基因上的GAA重复序列动态突变扩增所引起的,目前其不稳定性机制还不清楚。为了探索化学药物对GAA重复序列的作用,本实验构建了含有(GAA)42的重组质粒,转入大肠杆菌中,分别经过丝裂霉素C和甲基磺酸乙酯连续多次处理后,检测其长度变化发现,两种化学药物在不同程度上都可以促使(GAA)42发生删除,且删除后长度多数处于体内的正常范围。试验结果表明,化学药物可以促进与Friedreich共济失调相关的GAA重复序列发生删除。本工作为研究Friedreich共济失调的致病机理及治疗方案奠定了一定的基础。Friedreieh ataxia was caused by the expansion of a polymorphic and unstable GAA repeat sequences in the FRDA gene,but the mechanisms for its instability were poorly understood. In order to explore drugs effect on GAA repeat sequences,plasmid with （GAA）42was constructed and transformed in E. coli. The repeat sequences were detected after treated by MMC and EMS. It was found that two chemical drugs could result in the deletion of （GAA）42in different extent,and the repeat sequences length of being deleted was in normal range in vivo. The results showed that chemical drugs could promote deletion of GAA triplet repeat associated with friedreich ataxia. The work was the basis of further study of pathogenesis and treatment of friedreich ataxia.

关 键 词：GAA FRIEDREICH共济失调 丝裂霉素C 甲基磺酸乙酯 不稳定性 

分 类 号：R744.7[医药卫生—神经病学与精神病学]