Haston Christina K, Cory Sean, Lafontaine Laurie, Dorion Geneviève, Hallett Michael T
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Physiol Genomics. 2006 Apr 13;25(2):336-45. doi: 10.1152/physiolgenomics.00208.2005.
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.
除了疾病致病基因囊性纤维化跨膜传导调节因子（CFTR）外，未知的遗传因素也会影响囊性纤维化（CF）肺病的严重程度。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同源Cftr(-/-)（B6 CF）小鼠会发展为纤维化肺病。在本报告中，使用微阵列进行基因表达谱分析，以鉴定与非CF同窝小鼠相比，B6和BALB CF小鼠肺中差异表达的基因。在B6 CF和非CF对照肺之间，鉴定出702个基因或表达序列标签（EST）差异表达（P < 0.05），并且通过基因本体分类，B6 CF反应包括DNA代谢和有丝分裂的细胞增殖类别。在BALB小鼠对无功能Cftr的反应中，与对照相比，有943个基因/EST差异表达。凋亡以及T和B细胞增殖的生物学过程在BALB CF品系的基因列表中很突出。为支持这种品系差异，通过免疫组织化学染色发现，与B6 CF和非CF对照小鼠的肺相比，BALB CF小鼠肺中的T淋巴细胞浸润增加。在B6 CF和BALB CF小鼠之间，有444个基因/EST差异表达（P < 0.05，倍数> 2），其中56个定位于先前确定的连锁区间。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，包括免疫反应相关因素。
