Bleomycin-induced pulmonary fibrosis susceptibility genes in AcB/BcA recombinant congenic mice
Bleomycin-induced pulmonary fibrosis susceptibility genes in AcB/BcA recombinant congenic mice
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DOI：
10.1152/physiolgenomics.00095.2005
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发表时间：
2005-09-21
影响因子：
4.6
通讯作者：
Haston, CK
中科院分区：
文献类型：
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作者：
Lemay, AM;Haston, CK
肺纤维化易感性的遗传基础在很大程度上是未知的。最初，在这项研究中，使用一组从肺纤维化抗性A/J和易感C57 BL/6 J（B6）小鼠繁殖的重组同源品系，对调节博来霉素诱导的肺纤维化反应的基因座进行定位.在9号染色体上发现了连锁（比值分数的对数= 4.9），并检测到其他提示性位点。推定的基因座包括来自B6和A/J品系的等位基因，因为增加了同类小鼠的纤维化反应。基因表达谱芯片分析显示，博来霉素处理的B6和A/J小鼠肺组织中有3,304个基因或表达序列标签差异表达（P < 0.01），其中246个基因定位于潜在的易感基因位点。博莱霉素处理的B6和A/J小鼠之间的肺基因差异表达包括肝素结合和细胞外基质沉积途径。对现有基因组序列的回顾显示，连锁区间中有809个（占总数的43%）基因具有预测改变编码蛋白或其调节的变异，其中68个（8.4%）也差异表达。结合基因组方法以产生一组可能影响A/J：B6小鼠模型中对博来霉素诱导的肺纤维化的易感性的候选基因。
The genetic basis of susceptibility to pulmonary fibrosis is largely unknown. Initially, in this study, loci regulating the response of bleomycin- induced pulmonary fibrosis were mapped using a set of recombinant congenic strains bred from pulmonary fibrosis- resistant A/J and susceptible C57BL/6J (B6) mice. Linkage was identified (logarithm of the odds score = 4.9) on chromosome 9, and other suggestive loci were detected. The putative loci included alleles from both the B6 and A/J strains as increasing the fibrosis response of congenic mice. Gene expression analysis with microarrays revealed 3,304 genes or expressed sequence tags to be differentially expressed (P < 0.01) in lung tissue between bleomycin-treated B6 and A/J mice, and 246 of these genes mapped to potential susceptibility loci. Pulmonary genes differentially expressed between bleomycin- treated B6 and A/J mice included those of heparin binding and extracellular matrix deposition pathways. A review of available genomic sequences revealed 809 (43% of total) genes in the linkage intervals to have variations predicted to alter the encoded proteins or their regulation, 68 (8.4%) of which were also differentially expressed. Genomic approaches were combined to produce a set of candidate genes that may influence susceptibility to bleomycin- induced pulmonary fibrosis in the A/J: B6 mouse model.