长爪沙鼠脑缺血模型近交系的培育及发病机制研究
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国家自然科学基金项目(面上项目,重点项目,重大项目)


Establishment of a cerebral ischemia inbred Mongolian gerbil with its pathogenesis
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The National Natural Science Foundation of China (General Program, Key Program, Major Research Plan)

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    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基因及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,提高的研究结果可信度和稳定性,促进了相关机制研究。

    Abstract:

    The Mongolian gerbil has cerebral vascular variation,is a good laboratory animal model in cerebral ischemia research. However, the low successful rate affects the stability of research results and does not meet the welfare requirements.Our groupproved that the cerebral vascular variation is agenetic trait. Next, an ischemia-prone gerbil group was established by the through selecting and breeding. Our group bred cerebral ischemia inbred gerbilwith 76.62% animal missingcircle of Willis and 88.89% animal with cerebral ischemia byselectively inbreed by sister-brother mating. Themethodsof genetic monitor for inbred Mongolian gerbil were established base on biochemical loci and microsatellite DNA. Theinbred cerebral ischemia Mongolian gerbil characteristics of growth and development, blood physiology and biochemistry were analysis. It is a foundation for the application of this model. We found that VEGFA gene, and signal pathway of AKT/PI3Kand Notchare correlated with Mongolian gerbil cerebrovascular development.Moreover, four genes related to the development of cerebral blood vessels were screened by SHH. The cerebral ischemia inbred gerbil successfully solves the problem of model low incidence, reduce animal use, to improve reliability and stability of results, and promote the related mechanism. [Key words] Mongolian gerbil; cerebral ischemia; inbred; suppression subtractive hybridization

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李长龙,杜小燕,王东平,陈振文.长爪沙鼠脑缺血模型近交系的培育及发病机制研究[J].中国实验动物学报,,().

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  • 收稿日期:2018-06-10
  • 最后修改日期:2018-06-12
  • 录用日期:2018-06-19
  • 在线发布日期: 2018-11-12
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