降钙素基因相关肽转基因小鼠的建立及血压动态分析
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基金项目:

国家自然科学基金(31301932)。


Establishment and dynamic analysis of blood pressure in calcitonin gene-related peptide transgenic mice
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  • BAO Dan

    BAO Dan

    Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Peaking Union Medical College, Beijing 100021, China
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  • DONG Wei

    DONG Wei

    Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Peaking Union Medical College, Beijing 100021, China
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  • ZHANG Xu

    ZHANG Xu

    Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Peaking Union Medical College, Beijing 100021, China
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  • LIU Ning

    LIU Ning

    Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Peaking Union Medical College, Beijing 100021, China
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  • GAO Shan

    GAO Shan

    Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Peaking Union Medical College, Beijing 100021, China
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  • ZAHNG Hai-tao

    ZAHNG Hai-tao

    Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Peaking Union Medical College, Beijing 100021, China
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  • GAO Xiang

    GAO Xiang

    Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Peaking Union Medical College, Beijing 100021, China
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  • GE Wen-ping

    GE Wen-ping

    Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Peaking Union Medical College, Beijing 100021, China
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  • LV Dan

    LV Dan

    Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Peaking Union Medical College, Beijing 100021, China
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    摘要:

    目的 建立降钙素基因相关肽α(calcitonin gene-related peptide, CGRPα)和β(CGRPβ)转基因小鼠,并对其血压进行动态对比分析,建立可用于高血压研究的动物模型。方法 把人CGRPα和CGRPβ基因分别插入鸡β-肌动蛋白启动子下游,构建转基因表达载体,显微注射法建立C57BL/6J CGRPα和CGRPβ转基因小鼠,PCR鉴定转基因小鼠基因型。采用Western Blot鉴定CGRPα和CGRPβ在心脏、肺、肾脏和肝脏组织中的表达,筛选高表达转基因品系。用无创血压测量仪分析转基因小鼠动态血压变化。结果 建立了在心脏、肺、肾脏和肝脏组织中均高表达CGRPα基因的CGRPα转基因小鼠;在肺和肝脏组织中高表达CGRPβ基因的CGRPβ转基因小鼠。CGRPα转基因小鼠血压正常,CGRPβ转基因小鼠在12月龄时表现出显著的血压降低。结论 CGRPα和CGRPβ转基因小鼠可作为用于CGRP对外周血管阻力和高血压抵抗机制研究的动物模型。

    Abstract:

    Objective To establish calcitonin gene-related peptide α(CGRPα) and β(CGRPβ) transgenic mice and analyze dynamic changes of blood pressure using this transgenic mouse model in hypertension research. Methods The transgenic vector was constructed by inserting the human CGRPα and CGRPβ gene into the down steam of chicken β-actin promoter, respectively. The transgenic mice were created by microinjection. The genotype of transgenic line was identified by PCR and the expression level of target gene was determined by Western blot. Dynamic changes of blood pressure was measured by noninvasive blood pressure meter. Results One line of human CGRPα C57BL/6J transgenic mice with high levels of CGRPα expression in the heart, lung, kidney and liver tissues was established. One line of human CGRPβ C57BL/6J transgenic mice with high levels of CGRPβ expression in the lung and liver tissues was established. Mice overexpressing the human CGRPα were normotensive, whereas mice overexpressing the human CGRPβ were hypotensive at 12 months of age. Conclusions CGRPα and CGRPβ transgenic mice may serve as an animal model for the mechanism research on the roles of CGRP on peripheral vascular resistance and hypertension resistance.

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鲍丹,董伟,张旭,刘宁,高珊,张海涛,高翔,葛文平,吕丹.降钙素基因相关肽转基因小鼠的建立及血压动态分析[J].中国比较医学杂志,2015,25(10):11~16.

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  • 最后修改日期:2015-08-18
  • 在线发布日期: 2015-11-04
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