通过遗传多样性小鼠筛选EV71致病相关基因
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摘要
目的通过遗传多样性小鼠资源(Genetic Diversity Mice Resources)筛选肠道病毒71型(Enterovirus71,EV71)的致病相关基因,深入理解该病毒的致病机理,对临床诊断、治疗以及预后提供基础。方法 107copies EV71病毒经腹腔感染4～6周龄遗传多样性小鼠品系,收集血液和后肢骨骼肌样本,利用实时荧光定量PCR技术分析病毒载量,之后利用The Gene Mine系统遗传学数据库分析感染数据,筛选获得EV71致病相关基因。结果通过遗传多样性小鼠感染数据筛选到53个与EV71致病相关的基因。结论遗传多样性小鼠在模拟人群基因多样性、研究复杂性状疾病等方面具有较大的优势,是筛选致病相关基因理想的动物新资源。
Objective The aim of this study was to screen enterovirus 71( EV71) pathogenicity-related genes using genetic diversity mice to further understand the pathogenesis of the EV71,and lay the foundation for clinical diagnosis,treatment and prognosis. Methods Four-to-six week old genetic diversity mice were challenged with 107 copies of enterovirus 71 by intraperitoneal injection. The blood and hind limb skeletal muscles were collected,and the viral load was determined by real-time quantitative PCR. Then,the Gene Mine system genetic database was used to analyze the infection data,and EV71 pathogenicity-related genes were screened. Results Fifty-three genes related to EV71 infection were screened using genetic diversity mouse infection data. Conclusions Genetic diversity mice have significant advantages for simulating population genetic diversity and are a new resource to study complex trait diseases. Most importantly,they are an ideal and efficient resource for the screening of pathogenicity-related genes.
Objective The aim of this study was to screen enterovirus 71( EV71) pathogenicity-related genes using genetic diversity mice to further understand the pathogenesis of the EV71,and lay the foundation for clinical diagnosis,treatment and prognosis. Methods Four-to-six week old genetic diversity mice were challenged with 107 copies of enterovirus 71 by intraperitoneal injection. The blood and hind limb skeletal muscles were collected,and the viral load was determined by real-time quantitative PCR. Then,the Gene Mine system genetic database was used to analyze the infection data,and EV71 pathogenicity-related genes were screened. Results Fifty-three genes related to EV71 infection were screened using genetic diversity mouse infection data. Conclusions Genetic diversity mice have significant advantages for simulating population genetic diversity and are a new resource to study complex trait diseases. Most importantly,they are an ideal and efficient resource for the screening of pathogenicity-related genes.
引文
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[15] Zhao X,Sato A,Cruz CS,et al. CCL9 is secreted by the follicleassociated epithelium and recruits dome region Peyer’s patch CD11b+dendritic cells[J]. J Immunol,2003,171(6):2797-2803.
[2] Wang SM,Lei HY,Huang KJ,et al. Pathogenesis of enterovirus71 brainstem encephalitis in pediatric patients:roles of cytokines and cellular immune activation in patients with pulmonary edema[J]. J Infect Dis,2003,188(4):564-570.
[3]杨芳,于石成,张菊英,等. 2008—2011年我国大陆地区重症手足口病流行特征分析[J].疾病监测,2013,28(11):888-893.
[4]陈鑫,赵彬彬,武婧,等.手足口病从感染到发病的分子机制[J].中国比较医学杂志,2019,29(1):101-106.
[5] Chesler EJ,Miller DR,Branstetter LR,et al. The collaborative cross at Oak Ridge National Laboratory:developing a powerful resource for systems genetics[J]. Mamm Genome,2008,19(6):382-389.
[6] Iraqi FA, Churchill G, Mott R. The collaborative cross,developing a resource for mammalian systems genetics:a status report of the Wellcome Trust cohort[J]. Mamm Genome,2008,19(6):379-381.
[7] Ram R,Mehta M,Balmer L,et al. Rapid identification of major-effect genes using the collaborative cross[J]. Genetics,2014,198(1):75-86.
[8] Morahan G,Balmer L,Monley D. Establishment of“The Gene Mine”:a resource for rapid identification of complex trait genes[J]. Mamm Genome,2008,19(6):390-393.
[9] Zhang Y,Tan XJ,Wang HY,et al. An outbreak of hand,foot,and mouth disease associated with subgenotype C4 of human enterovirus 71 in Shandong,China[J]. J Clin Virol,2009,44(4):262-267.
[10] Yang CF,De L,Yang SJ,et al. Genotype-specific in vitro amplification of sequences of the wild type 3 polioviruses from Mexico and Guatemala[J]. Virus Res,1992,24(3):277-296.
[11] Rogala AR, Morgan AP, Christensen AM, et al. The collaborative cross as a resource for modeling human disease:CC011/Unc,a new mouse model for spontaneous colitis[J].Mamm Genome,2014,25(3-4):95-108.
[12] Rasmussen AL,Okumura A,Ferris MT,et al. Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance[J]. Science,2014,346(6212):987-991.
[13] Geserick P,Kaiser F,Klemm U,et al. Modulation of T cell development and activation by novel members of the Schlafen(slfn)gene family harbouring an RNA helicase-like motif[J].Int Immunol,2004,16(10):1535-1548.
[14] Nakagawa K,Matsuki T,Zhao L,et al. Schlafen-8 is essential for lymphatic endothelial cell activation in experimental autoimmune encephalomyelitis[J]. Int Immunol,2018,30(2):69-78.
[15] Zhao X,Sato A,Cruz CS,et al. CCL9 is secreted by the follicleassociated epithelium and recruits dome region Peyer’s patch CD11b+dendritic cells[J]. J Immunol,2003,171(6):2797-2803.