Identification of therapeutic drug target genes by "genome-wide" expression profile analysis on animal models of human disease

基因组科学的出现极大地改变了包括医学调查在内的生命科学研究的方式，因此需要“系统的”和“综合的”方法(即所谓的“全基因组”调查)。现在，全基因组转录组和蛋白质组扫描正在成为可能。“基因组-转录组-蛋白质组学”的趋势是合乎逻辑的，在每个方面，功能基因组学的方法现在都在以很快的速度进行；然而，仍然是标准化的方法还不成熟或缺乏。近年来，以基因组为基础的新型基因芯片、DNA芯片等技术不断创新，并迅速应用于医学研究。基因微阵列或DNA芯片技术允许同时监测成百上千个基因的表达，并提供一种识别基因及其活性变化的格式。微阵列可以从特定的感兴趣的cDNA克隆、cDNA文库或从基因组测序数据库中选择数量的开放阅读片段构建，以允许对表达序列进行大规模的功能分析。利用DNA微阵列等新的基因组学工具分析疾病状态和药物治疗，可以识别药物靶点，提高开发有效治疗药物的几率，从而为发育生物学的研究提供一种新的途径。作为验证该系统的模型系统，我们在抗肾小球基底膜血清诱导的肾炎大鼠模型中检测了GN的进展。基因芯片分析确定了与疾病相关的差异表达基因，这些基因似乎是潜在的重要治疗靶点。

The advent of Genome Science had markedly changed the way how the life science research including.medical investigation is conducted; thus, "systematic" and "integrated" approach is required (so called "genome-wide" survey). Now, genome-wide transcriptome and proteomics scanning are becoming feasible. The stream of "Genome -Trariscriptome -Proteomics" is logical, and in each aspect approaches for functional genomics are now pursued at a high pace; however, still standardized approach is immature or lacking. Very recently, novel genome-based technology of cDNA microarray, DNA chips has been innovated and immediately applied for the medical researches. The cDNA microarray or DNA-chip technology allows expression monitoring of hundreds and thousands of genes simultaneously and provides a format for,identifying genes as well as changes in their activity. Microarrays can be constructed from specific cDNA clones of interest, a cDNA library, or a select number of open reading fragments from a genome sequencing database to allow a large-scale functional analysis of expressed sequences. Analyzing disease states and drug treatment with the new tools of genomics such as DNA microarray enables the identification of drug targets and should improve the odds of developing useful therapeutics, thereby it would provide a new approach to investigations in developmental biology. As a model system to verify the system, we examined the progression of GN in a rat model of anti-glomerular basement membrane serum-induced nephritis. cDNA microarray analysis identified disease-related, differentially expressed gene, which appear to be potentially important therapeutic targets.