Rosa26位点定点敲入hSCARB2基因小鼠的生理生化及心脏功能表型分析OA
Phenotypic characterization of hematological,biochemical,and cardiac parameters in Rosa26-targeted hSCARB2 knock-in mice
目的 以 CRISPR/Cas9 技术构建的 Rosa26 位点 hSCARB2 基因定点敲入小鼠为研究对象,系统检测其血液生理、血清生化及心电图参数,分析性别和基因型对上述指标的影响,为该模型在肠道病毒相关研究中的应用提供基础数据.方法 选取 8 周龄 hSCARB2 KI 小鼠和野生型小鼠各 10 只,雌雄各半.采集静脉血,检测18 项血液生理指标与15 项血清生化指标,并同步记录心电图.采用独立样本t 检验比较性别间及基因型间的差异.结果 hSCARB2 KI 小鼠所测 18 项血液生理指标无性别差异(P>0.05);15 项生化指标中仅雄性小鼠的白蛋白(ALB)高于雌性(P<0.05).与野生型小鼠相比,hSCARB2 KI 小鼠白细胞数目(WBC)和淋巴细胞数目(Lymph)降低(P<0.05),血红蛋白(HGB)浓度升高(P<0.01);生化指标中谷草转氨酶(AST)降低(P<0.01),肌酐(CREA)升高(P<0.01),总胆红素(TBIL)、总胆汁酸(TBA)及乳酸脱氢酶同工酶(LDH1)升高(P<0.05).两组心电图及心率无显著差异(P>0.05).结论 hSCARB2 基因定点敲入仅引起血液系统相关指标的轻微变化,以及脂质代谢和肾脏排泄相关生化指标的生理性适应,对基础心脏电生理功能无明显影响.该模型生理状态稳定,可为肠道病毒感染机制研究、疫苗评价及抗病毒药物筛选提供可靠的实验动物平台与基础数据支撑.
Objective Using CRISPR/Cas9 technology-generated Rosa26 locus hSCARB2 gene targeted knock-in mice as the research subjects,this study systematically measured their blood physiological parameters,serum biochemical indices,and electrocardiographic parameters,and analyzed the effects of sex and genotype on these indicators,so as to provide baseline data for the application of this model in enterovirus-related research.Methods Venous blood was collected from 8 weeks old hSCARB2 knock-in(KI)mice(n=10)and wild-type littermates(n=10),with equal numbers of males and females,to measure 18 hematological and 15 serum biochemical parameters.Electrocardiograms were recorded at the same time point.Independent-samples t-tests were used to compare sex and genotype-related differences.Results No significant sex differences were observed in the hematological parameters(P>0.05).Among the 15 biochemical parameters,only serum albumin was slightly higher in male than female hSCARB2 KI mice(P<0.05).Compared with wild-type mice,hSCARB2 KI mice exhibited lower white blood cell and lymphocyte counts(P<0.05),higher hemoglobin concentrations(P<0.01),lower aspartate aminotransferase levels(P<0.01),and higher serum creatinine(P<0.01),total bilirubin,total bile acid,and lactate dehydrogenase-1 levels(all P<0.05).Electrocardiographic parameters and heart rate did not differ significantly between genotypes(P>0.05).Conclusions Targeted KI of hSCARB2 at the Rosa26 locus did not cause significant organ damage in mice,resulting only in modest changes in hematological parameters and biochemical markers related to in lipid metabolism and renal excretion,without affecting baseline cardiac electrophysiological function.These findings indicate that this model has a stable physiological phenotype and may provide a reliable experimental platform for mechanistic studies of enterovirus pathogenesis,vaccine evaluation,and antiviral drug screening.
黄真;黄璋琼;申红;叶尤松;李哲丽;龙维虎;刘妙;王子鸥;蒋博伟;范胜涛
中国医学科学院医学生物学研究所,昆明 650031中国医学科学院医学生物学研究所,昆明 650031中国医学科学院医学生物学研究所,昆明 650031中国医学科学院医学生物学研究所,昆明 650031中国医学科学院医学生物学研究所,昆明 650031中国医学科学院医学生物学研究所,昆明 650031中国医学科学院医学生物学研究所,昆明 650031中国医学科学院医学生物学研究所,昆明 650031中国医学科学院医学生物学研究所,昆明 650031中国医学科学院医学生物学研究所,昆明 650031
生物科学
hSCARB2 KI小鼠转基因小鼠模型生理生化
hSCARB2 KI micetransgenic mouse modelphysiologybiochemistry
《中国比较医学杂志》 2026 (16)
67-74,8
国家自然科学基金联合基金项目(U2202214)科技创新2030重大项目(2023ZD0406306)云南省医学学科带头人培养计划(D-2024006)云南省生物药转化与评价技术创新中心(202505AK340009).
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