遗传多样性高血压小鼠模型的建立与基因转录调控分析OA北大核心CSTPCD
Establishment of a genetically diverse mouse model of hypertension and analysis of gene transcription regulation
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 blood pressure,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.
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 of Cckbr+/+,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-/-and Cckbr+/+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.
黄智滨;潘吉荣;张伶燕;赵大路;王谦;魏承志;马旭;白琳;秦川
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||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||昌平实验室(CPNL),北京 102206||呼吸健康与共病国家重点实验室,北京 100005
生物学
遗传多样性小鼠Cckbr原发性高血压动物模型
genetically diverse mouseCckbressential hypertensionanimal model
《中国实验动物学报》 2024 (005)
576-584 / 9
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).Funded by CAMS Initiative for Innovative Medicine of China(2021-I2M-1-034),National Key R&D Program of China(2021YFF0703200).
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