Diarrhea as a cause of mortality in a mouse model of infectious colitis.

Diarrhea as a cause of mortality in a mouse model of infectious colitis.
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腹泻是传染性结肠炎小鼠模型中死亡率的原因。

DOI:
10.1186/gb-2008-9-8-r122
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发表时间:
2008
期刊:
影响因子:
12.3
通讯作者:
Schauer, David B.
Schauer, David B.
中科院分区:
生物学1区
文献类型:
--
作者:
Borenshtein, Diana;Fry, Rebecca C.;Groff, Elizabeth B.;Nambiar, Prashant R.;Carey, Vincent J.;Fox, James G.;Schauer, David B.

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对感染柠檬酸杆菌的易感和抗性小鼠结肠中基因表达的分析表明,死亡率与肠道离子转运受损有关。 感染期间全基因组转录变化的比较特征可有助于阐明宿主易感性的潜在机制。在这项研究中,对两种同源小鼠品系的小鼠结肠进行了转录图谱分析,这两种小鼠对柠檬酸杆菌感染的反应不同;易感的近交系FVB/N小鼠和抗性的远交系瑞士 Webster小鼠。在感染前以及接种后4天和9天,使用全小鼠基因组Affymetrix芯片测定远端结肠中的基因表达。 计算分析确定了462个探针组,在未接种的抗性和易感小鼠之间差异表达超过2倍。针对柠檬酸杆菌感染,5123个探针组在一种或两种小鼠品系中差异表达。通过对35个选定基因进行定量实时RT - PCR验证了微阵列数据,发现符合率为94%。由1547个探针组代表的转录本在易感和抗性小鼠之间差异表达,与感染状态无关,这是一种宿主效应。与转运相关的基因比甚至免疫反应相关基因的过度表达程度更高。电解质分析显示易感动物血清中氯和钠的水平降低。 这些结果支持以下假设:感染柠檬酸杆菌的易感小鼠的死亡率与肠道离子转运受损以及致命性液体流失和脱水的发展有关。这些研究有助于我们理解柠檬酸杆菌的发病机制,并为预防和治疗与肠道细菌感染相关的腹泻提出了新的策略。
Analysis of gene expression in the colons of Citrobacter rodentium-infected susceptible and resistant mice suggests that mortality is associated with impaired intestinal ion transport. Comparative characterization of genome-wide transcriptional changes during infection can help elucidate the mechanisms underlying host susceptibility. In this study, transcriptional profiling of the mouse colon was carried out in two cognate lines of mice that differ in their response to Citrobacter rodentium infection; susceptible inbred FVB/N and resistant outbred Swiss Webster mice. Gene expression in the distal colon was determined prior to infection, and at four and nine days post-inoculation using a whole mouse genome Affymetrix array. Computational analysis identified 462 probe sets more than 2-fold differentially expressed between uninoculated resistant and susceptible mice. In response to C. rodentium infection, 5,123 probe sets were differentially expressed in one or both lines of mice. Microarray data were validated by quantitative real-time RT-PCR for 35 selected genes and were found to have a 94% concordance rate. Transcripts represented by 1,547 probe sets were differentially expressed between susceptible and resistant mice regardless of infection status, a host effect. Genes associated with transport were over-represented to a greater extent than even immune response-related genes. Electrolyte analysis revealed reduction in serum levels of chloride and sodium in susceptible animals. The results support the hypothesis that mortality in C. rodentium-infected susceptible mice is associated with impaired intestinal ion transport and development of fatal fluid loss and dehydration. These studies contribute to our understanding of the pathogenesis of C. rodentium and suggest novel strategies for the prevention and treatment of diarrhea associated with intestinal bacterial infections.
DOI: 10.1093/bioinformatics/btg455
发表时间: 2004-03-01
期刊: BIOINFORMATICS
影响因子: 5.8
作者:
Al-Shahrour, F;Díaz-Uriarte, R;Dopazo, J
通讯作者: Dopazo, J
DOI: 10.1152/ajpgi.00332.2003
发表时间: 2004-07-01
影响因子: 4.5
作者:
Bachmann, O;Riederer, B;Seidler, U
通讯作者: Seidler, U
DOI: 10.1128/iai.01810-06
发表时间: 2007-07-01
影响因子: 3.1
作者:
Borenshtein, Diana;Nambiar, Prashant R.;Schauer, David B.
通讯作者: Schauer, David B.
DOI: 10.1152/ajplung.2002.282.1.l12
发表时间: 2002-01-01
影响因子: 4.9
作者:
Cobb, BR;Ruiz, F;Clancy, JP
通讯作者: Clancy, JP
DOI: 10.1152/ajpgi.00484.2001
发表时间: 2002-07-01
影响因子: 4.5
作者:
Crane, JK;Olson, RA;Duffey, ME
通讯作者: Duffey, ME