Strain-dependent pulmonary gene expression profiles of a cystic fibrosis mouse model
Strain-dependent pulmonary gene expression profiles of a cystic fibrosis mouse model
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DOI：
10.1152/physiolgenomics.00208.2005
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发表时间：
2006-04-13
影响因子：
4.6
通讯作者：
Hallett, MT
中科院分区：
文献类型：
--
作者：
Haston, CK;Cory, S;Hallett, MT
囊性纤维化（CF）肺部疾病严重程度除受致病基因囊性纤维化跨膜传导调节因子（CFTR）影响外，还受未知遗传因素的影响。先前的研究表明，与BALB/c背景的CF小鼠和野生型动物相比，C57BL/6J基因Cftr(-/-) （B6 CF）小鼠可发生纤维化肺疾病。在本报告中，基因表达谱与微阵列被用于鉴定基因在B6和BALB CF小鼠与非CF窝鼠肺中的差异表达。在B6 CF与非CF对照肺中鉴定出772个基因或表达序列标签（est）差异表达（P < 0.05），通过Gene Ontology分类，B6 CF应答包括DNA代谢和有丝分裂的细胞增殖类别。在BALB小鼠对无功能Cftr的应答中，943个基因/ ESTs与对照组相比存在差异表达。在BALB CF菌株的基因列表中，细胞凋亡和T细胞和B细胞增殖的生物学过程是突出的。通过免疫组化染色，与B6 CF和非CF对照小鼠的肺相比，BALB CF小鼠肺中T淋巴细胞浸润明显增加，支持这种菌株差异。444个基因/ ESTs在B6 CF和BALB CF小鼠之间存在差异表达（P < 0.05, fold bbb2），其中56个基因/ ESTs与先前确定的连锁区间相关。这些结果表明，该小鼠模型中CF肺病的可变严重程度受多种遗传因素控制，包括免疫反应的遗传因素。
Cystic fibrosis (CF) lung disease severity is influenced by unknown genetic factors apart from the disease causative gene, cystic fibrosis transmembrane conductance regulator ( CFTR). Previous studies have shown the C57BL/6J congenic Cftr(-/-) (B6 CF) mouse to develop a fibrotic lung disease compared with both CF mice of the BALB/c background and wild-type animals. In this report, gene expression profiling with microarrays was used to identify genes differentially expressed in the lungs of B6 and BALB CF mice compared with non-CF littermates. Seven hundred two genes or expressed sequence tags ( ESTs) were identified to be differentially expressed between the B6 CF and non-CF control lungs ( P < 0.05), and, by Gene Ontology classification, the B6 CF response included the cell proliferation categories of DNA metabolism and mitosis. In the response of BALB mice to nonfunctional Cftr, 943 genes/ ESTs were differentially expressed compared with controls. The biological processes of apoptosis and T and B cell proliferation were prominent in the gene list of the BALB CF strain. In support of this strain difference, increased T lymphocyte infiltration was evident in the lungs of BALB CF mice, through immunohistochemical staining, compared with the lungs from both B6 CF and non-CF control mice. Four hundred forty-four genes/ ESTs were differentially expressed between B6 CF and BALB CF mice ( P < 0.05, fold > 2), including 56 that map to previously identified linkage intervals. These results suggest that the variable severity of CF lung disease in this mouse model is controlled by multiple genetic factors, including those of an immune response.