Identification and Characterization of microRNA Genes in Asthma

MicroRNAs是一种小的、22个核苷酸长的非编码RNA，它通过与靶基因的3个非编码区结合来调节基因的表达，从而导致蛋白质翻译的抑制和mRNA稳定性的降低。在这里，我们假设microRNAs调节哮喘的发病机制。利用全基因组肺microRNA转录组的筛选来鉴定在室内尘螨诱发哮喘的实验小鼠模型中其表达发生改变的microRNAs。此外，还评估了皮质类固醇治疗对microRNA表达的影响。目前正在进行的工作是培育有条件地表达或删除肺细胞中候选microRNA基因的小鼠。我们已经产生了一只过度表达候选microRNA基因之一的转基因小鼠，目前正在利用该基因来表征其在哮喘发病机制中的作用。我们还创建了一个质粒来产生一个条件基因敲除小鼠，以获得另一个候选microRNA基因，该基因可能调节哮喘的致病表现。

MicroRNAs are small, 22 nucleotide-long, non-coding RNAs that regulate gene expression via binding to the 3 UTR of target genes, which results in the suppression of protein translation and decreased mRNA stability. Here, we hypothesized that microRNAs modulate the pathogenesis of asthma. A genome wide screen of the lung microRNA transcriptome was utilized to identify microRNAs whose expression is altered in an experimental murine model of house dust mite-induced asthma. In addition, the effect of corticosteroid treatment on microRNA expression was assessed. Ongoing work is directed at generating mice that conditionally express or delete candidate microRNA genes in lung cells. We have generated a transgenic mouse that over-expresses one of the candidate microRNA genes, which is currently being utilized to characterize its role in the pathogenesis of asthma. We have also created a plasmid to generate a conditional knock-out mouse for an additional candidate microRNA gene that may modulate the pathogenic manifestations of asthma.