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转基因小鼠人载脂蛋白AI基因表达对血浆高密度脂蛋白的影响

更新时间:2012-10-15 14:46:20  
李汇华 谷素敏 佘铭鹏

  【摘要】 目的 研究载脂蛋白AI(apoAI)基因表达调控对血浆高密度脂蛋白(HDL)代谢的影响。方法 采用已建立的含小鼠金属硫蛋白I(MT-I)启动子的人apoAI转基因C57BL/6小鼠系,通过Southern及Northern杂交技术检测锌诱导前后人apoAI基因整合和表达的情况。结果 转基因小鼠整合4~15拷贝的人apoAI基因。人apoAI基因主要在肝和肾中表达,经重金属锌诱导后,人apoAI基因可在肝、小肠及肾中高效表达。转基因鼠血浆总apoAI水平比对照组明显增高,其中人apoAI水平经锌诱导后增高约46%。与对照组相比,血浆HDL水平在锌诱导前后分别增高约47%和103%。转基因鼠HDL和人apoAI水平间呈显著正相关(r=0.85,P<0.01)。结论 ApoAI对血浆HDL水平升高有重要的调节作用,该转基因鼠是进一步研究apoAI在高脂血症时对脂质代谢的影响和抗动脉粥样硬化(AS)作用机制的理想动物模型。
  【关键词】 小鼠,转基因  载脂蛋白A-I  脂蛋白类,HDL

  The effect of expressed human apolipoprotein AI on plasma high density lipoprotein level in transgenic mice Li Huihua,Gu Sumin, She Mingpeng.Department of Pathology, Institute of Basic Medical Sciences, PUMC & CAMS , Beijing 100005
  【Abstract】 Objective To study the regulation of human apolipoprotein AI(h-apo AI) gene expression and its role in high density lipoprotein (HDL) metabolism. Methods Transgenic C57BL/6 mice established in this laboratory with human apoAI gene containing mouse metallothionein-I(MT-I)promoter were used for investigation. Results Southern blot identified the presence of 4~15 copies of h- apo AI gene in the transgenic mice. Northern blot showed that human apo AI mRNA was expressed mainly in the liver and kidneys, and the high level of h-apo AI mRNA was obtained in liver, kidneys and small intestine after Zinc(Zn) induction. Total Plasma apoAI Level in transgenic mice was significantly increased than that in the controls, and a high h-apoAI level was detected in the transgenic mice (46% increased after Zn induction). Additionally, total and HDL cholesterol levels were noticed to be highly increased to 47% before and 103% after Zn induction in the transgenic mice comparing to that of the controls. The plasma HDL and h-apoAI levels were significantly correlated (r=0.85, P<0.01) in the transgenic mice. Conclusion Apo AI has a profound effect on regulating HDL levels in the transgenic mice. This animal model is considered a

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