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李长龙,杜小燕,王冬平,陈振文.长爪沙鼠脑缺血模型近交系的培育及其发病机制研究进展[J].中国实验动物学报,2018,26(4):512~517.
长爪沙鼠脑缺血模型近交系的培育及其发病机制研究进展
Advances in research of the establishment of an inbred Mongolian gerbil model of cerebral ischemia and its mechanism of pathogenesis
投稿时间:2018-06-10  
DOI:10.3969/j. issn. 1005 - 4847. 2018. 04. 017
中文关键词:  长爪沙鼠  脑缺血  近交系  抑制消减杂交
英文关键词:Mongolian gerbil  cerebral ischemia  inbred  suppression subtractive hybridization
基金项目:国家科技支撑计划(No. 2015BAI09B01);国家自然科学基金(No. 31572348,No. 31572341,No. 31772545)
作者单位E-mail
李长龙 首都医科大学基础医学院,北京 100069 li?changlong@126. com 
杜小燕 首都医科大学基础医学院,北京 100069  
王冬平 军事医学研究院实验动物中心,北京 100071  
陈振文 首都医科大学基础医学院,北京 100069 czwen@ ccmu. edu. Cn 
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中文摘要:
      长爪沙鼠具有脑血管变异缺失的特性,是脑缺血研究良好的模型动物?普通长爪沙鼠群体中模型成功率低,影响研究结果稳定性,不符合实验动物福利要求?我们团队在证实脑血管Willis 环(circle of Willis, COW)变异缺失具有遗传性的基础上,首先通过定向选育建立了脑缺血高发群体,进而通过全同胞近亲繁殖的方式,建立了脑缺血模型近交系,其COW 缺失率达76. 62%,模型成功率达到88. 89%?此外,建立了近交系微卫星DNA 和生化位点遗传检测方法,分析了长爪沙鼠脑缺血模型近交系动物的生长发育和血液生理生化等指标,为该模型的推广应用奠定了基础?我们还发现,VEGFA 基因?AKT/ PI3K 和Notch 信号通路在长爪沙鼠脑血管发育中发挥重要作用?通过抑制消减杂交方法筛选获得4 个与长爪沙鼠脑血管发育相关的基因?长爪沙鼠脑缺血模型近交系的培育成功解决了模型发生率低的问题,减少了动物使用量,提高了研究结果可信度和稳定性,促进了相关机制研究?
英文摘要:
      Mongolian gerbil has cerebral vascular variation. It is a good laboratory animal model in cerebral ischemia research. However, the low successful rate affects the stability of research result and does not meet the animal welfare requirements. Our group proved that the cerebral vascular variation is a genetic trait. Next, an ischemia?prone gerbil group was established by the through selecting and breeding. Our group bred a cerebral ischemia inbred gerbil with 76. 62% of animals missing circle of Willis and 88. 89% of animals with cerebral ischemia by selectively inbreed by sister?brother mating. The method of genetic monitor for inbred Mongolian gerbil were established based on biochemical loci and microsatellite DNA. The characteristics of growth and development, blood physiology and biochemistry of the inbred cerebral ischemia Mongolian gerbil were analyzed, which provides a foundation for the application of this model. We found that VEGFA gene, and signal pathway of AKT/ PI3K and Notch are correlated with Mongolian gerbil cerebrovascular development. Moreover, four genes related to the development of cerebral blood vessels were screened by suppression subtractive hybridization ( SHH). The cerebral ischemia inbred gerbil successfully solves the problem of model low incidence, reduces animal use, improves the reliability and stability of result, and promotes the related research of its mechanism.
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