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Regulation of dopamine levels by transgene expression in rat models of Parkinson's disease
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- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF NEUROMEDICINE
- Issue:
- 12
- DOI:
- 10.3760/cma.j.issn.1671-8925.2007.12.003
- Key Word:
- 帕金森病;腺相关病毒;基因调控;Cre重组酶;多巴胺
Abstract： 目的 究设计一种病毒载体介导的体内调节系统,依据诱导性Cre重组酶来调控转基因治疗帕金森病大鼠的基因表达.方法 将重组腺相关病毒(AAV)载体表达的Cre重组酶融合到雌激素受体的配体结合区,与AAV载体表达的多巴胺合成酶一起转导到帕金森病大鼠模型中.用合成的雌激素受体调节剂他莫昔芬处理.结果 诱导位于LoxP侧面的酪氨酸羟化酶(TH)序列选择性的敲掉,导致多巴胺的合成减少,而芳香族氨基酸脱羧酶(AADC)的表达不受影响,从而保持左旋多巴的疗效.结论 病毒载体介导的诱导性的Cre重组酶在体内的应用可作为一种分子开关,对转基因表达进行时空调控,从而增加基因治疗的安全性.
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