遗传多样性高血压小鼠模型的建立与基因转录调控分析
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作者单位:

1. 中国医学科学院北京协和医学院医学实验动物研究所,北京 100021;2. 国家人类疾病动物模型资源库,国家卫生健康委员会人类疾病比较医学重点实验室,新发与再发传染病动物模型研究北京市重点实验室,北京市人类重大疾病动物模型工程技术研究中心,国家动物模型技术创新中心,北京 100021;3. 昌平实验室(CPNL),北京 102206;4. 呼吸健康与共病国家重点实验室,北京 100005


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

1. Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing 100021, China; 2. National Human Diseases Animal Model Resource Center, NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory of Animal Models of Emerging and Re-Emerging Infectious Diseases, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, National Animal Model Technology Innovation Center, Beijing 100021, China; 3. Changping Laboratory, Beijing 102206, China;4. State Key Laboratory of Respiratory Health and Multimorbidity, Beijing 100005, China

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    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- / -3 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 CCKBR蛋白表达变化,利用苏木素-伊红(HE)染色、免疫组化( IHC)检测小鼠肾组织病理学变化,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( systolic bloodpressure,SBP)Cckbr- / -组较 Cckbr+ / +组具有显著性差异( P<0. 05)。 HE 染色及 IHC 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。 结论遗传多样性高血压小鼠在血压表型、病理特征及基因表达等方面呈现显著性差异,有效模拟了人群的遗传异质性对疾病表型的影响。

    Abstract:

    Objective To investigate the differences in blood pressure phenotypes, renal pathological changes, and related pathogenic pathways in genetically diverse hypertensive mice obtained from 13 strains. Methods The genotypes ofCckbr+ / +,Cckbr+ / -and Cckbr- / -were obtained by hybridization of 13 strains of genetically diverse mice with Cckbr- / - mice. Blood pressure was measured with a noninvasive blood pressure analysis system (BP-2000). The expression of CCKBR protein in mouse kidney tissue was detected by Western Blot, and the pathological changes in mouse kidney tissue were detected by hematoxylin-eosin ( HE) staining and immunohistochemistry ( IHC). The pathogenic pathways related to essential hypertension were screened by RNA sequencing. Results In three specific mouse strains (A/ J, LOT,and FIM), the systolic blood pressure( SBP) was significantly different between the Cckbr- / -andCckbr+ / + groups. HE staining and IHC showed that hypertension caused a certain degree of renal injury in the mice. Gene Ontology(GO) and pathway enrichment analysis showed that differentially expressed genes were enriched in metabolic processes and circadian rhythm regulation. Conclusions Genetically diverse mice can effectively simulate the genetic background of the population and provide a new resource for studying the pathogenic genes related to essential hypertension.

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黄智滨,潘吉荣,张伶燕,赵大路,王谦,魏承志,马旭,白琳,秦川.遗传多样性高血压小鼠模型的建立与基因转录调控分析[J].中国实验动物学报,2024,32(5):576~584.

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  • 收稿日期:2024-02-21
  • 在线发布日期: 2024-06-24
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