Brudzewsky D, Pedersen A E, Claesson M H, Gad M, Kristensen N N, Lage K, Jensen T, Tommerup N, Larsen L A, Knudsen S, Tümer Z
Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Scand J Immunol. 2009 May;69(5):437-46. doi: 10.1111/j.1365-3083.2009.02243.x. Epub 2009 Feb 26.
Inflammatory bowel disease (IBD) is a multifactorial disorder with an unknown aetiology. The aim of this study is to employ a murine model of IBD to identify pathways and genes, which may play a key role in the pathogenesis of IBD and could be important for discovery of new disease markers in human disease. Here, we have investigated severe combined immunodeficient (SCID) mice, which upon adoptive transfer with concanavalin A-activated CD4(+) T cells develop inflammation of the colon with predominance in rectum. Mice with increasing level of inflammation was studied. RNA from rectum of transplanted and non-transplanted SCID mice was investigated by a genome-wide gene expression analysis using the Affymetrix mouse expression array 430A (MOE430A) including 22,626 probe sets. A significant change in gene expression (P = 0.00001) is observed in 152 of the genes between the non-transplanted control mice and colitis mice, and among these genes there is an overrepresentation of genes involved in inflammatory processes. Some of the most significant genes showing higher expression encode S100A proteins and chemokines involved in trafficking of leucocytes in inflammatory areas. Classification by gene clustering based on the genes with the significantly altered gene expression corresponds to two different levels of inflammation as established by the histological scoring of the inflamed rectum. These data demonstrate that this SCID T-cell transfer model is a useful animal model for human IBD and can be used for suggesting candidate genes involved in the pathogenesis and for identifying new molecular markers of chronic inflammation in human IBD.
炎症性肠病（IBD）是一种病因不明的多因素疾病。本研究的目的是利用IBD小鼠模型来确定可能在IBD发病机制中起关键作用且对发现人类疾病新的疾病标志物具有重要意义的信号通路和基因。在此，我们研究了严重联合免疫缺陷（SCID）小鼠，其在接受伴刀豆球蛋白A激活的CD4(+) T细胞过继转移后会发生以直肠为主的结肠炎症。对炎症程度不断增加的小鼠进行了研究。使用包含22,626个探针集的Affymetrix小鼠表达阵列430A（MOE430A），通过全基因组基因表达分析对移植和未移植的SCID小鼠直肠中的RNA进行了研究。在未移植的对照小鼠和结肠炎小鼠之间，152个基因的基因表达出现了显著变化（P = 0.00001），其中参与炎症过程的基因出现了过度表达。一些表达较高的最显著基因编码S100A蛋白和参与白细胞在炎症区域迁移的趋化因子。基于基因表达显著改变的基因进行基因聚类分类，与通过炎症直肠的组织学评分确定的两种不同炎症水平相对应。这些数据表明，这种SCID T细胞转移模型是一种用于人类IBD的有用动物模型，可用于提示参与发病机制的候选基因，并用于识别人类IBD中慢性炎症的新分子标志物。
