遗传多样性高血压小鼠模型的建立与基因转录调控分析
DOI:
CSTR:
作者:
作者单位:

医学实验动物研究所

作者简介:

通讯作者:

中图分类号:

基金项目:

中国医学科学院医学与健康科技创新工程(2021-I2M-1-034),国家重点研发计划(2021YFF0703200)。


Establishment of a genetically diverse hypertensive mouse model and analysis of gene transcription regulation
Author:
Affiliation:

1.Institute of Laboratory Animals Science,CAMS &2.PUMC

Fund Project:

CAMS initiative for Innovative Medicine of China (2021-I2M-1-034),National Key R D Program of China(2021YFF0703200).

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的 探讨13个品系的遗传多样性高血压小鼠的血压表型差异、肾脏病理变化以及相关致病通路。方法 将13个品系的遗传多样性小鼠分别与Cckbr-/-小鼠进行杂交,得到不同遗传背景的Cckbr+/+Cckbr+/-Cckbr-/-三种基因型的小鼠。利用BP-2000无创血压分析系统测量小鼠血压,利用Western blot检测小鼠肾脏CCKBR蛋白表达变化,利用HE染色、免疫组化(IHC)检测小鼠肾脏组织病理学变化,利用转录组测序(RNA-Seq)分析筛选原发性高血压致病相关通路。结果 3个特定小鼠品系(A/J、LOT、FIM)中,收缩压(SBP)Cckbr-/-较Cckbr+/+有显著差异(P<0.05)。HE染色及免疫组化发现高血压对小鼠造成了一定程度的肾损伤。通过GO与Pathway富集分析发现差异表达基因富集在新陈代谢与昼夜节律调节等方面。结论 遗传多样性小鼠可以更好地模拟人群的遗传背景,为研究原发性高血压相关致病基因提供了新的资源。

    Abstract:

    Objective To investigate the differences in blood pressure phenotype, renal pathological changes and related pathogenic pathways in genetically diverse hypertensive mice from 13 strains. Methods The mice with different genotypes were obtained by crossing 13 genetically diverse strains with Cckbr-/- mice, and then the blood pressure was measured by BP-2000 noninvasive blood pressure analysis system, the expression of CCKBR protein in mice kidney was detected by Western blot, the pathological changes of mice kidney tissue were detected by HE staining and immunohistochemistry (IHC), and the pathogenic pathways related to essential hypertension were screened by RNA-Seq. Results In 3 specific mouse strains (A/J, LOT, FIM), the systolic blood pressure (SBP) of Cckbr-/- group was significantly different from that of Cckbr+/+ group. HE staining and immunohistochemistry showed that hypertension caused a certain degree of renal injury in mice. GO and Pathway enrichment analysis showed that differentially expressed genes were enriched in metabolism and circadian rhythm regulation. Conclusion Genetically diverse mice can better simulate the genetic background of the population and provide a new resource for studying the pathogenic genes related to essential hypertension.

    参考文献
    相似文献
    引证文献
引用本文
分享
相关视频

文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2024-02-21
  • 最后修改日期:2024-05-06
  • 录用日期:2024-05-11
  • 在线发布日期:
  • 出版日期:
文章二维码
防诈骗提示!请勿点击不明链接或添加个人微信。编辑部所有邮箱后缀均为@cnilas.org
关闭