Modulation of intestinal gene expression by dietary zinc status: Effectiveness of cDNA arrays for expression profiling of a single nutrient deficiency
Modulation of intestinal gene expression by dietary zinc status: Effectiveness of cDNA arrays for expression profiling of a single nutrient deficiency
复制标题
DOI：
10.1073/pnas.251532498
复制
发表时间：
2001-11-20
影响因子：
11.1
通讯作者：
Cousins, RJ
中科院分区：
文献类型：
--
作者：
Blanchard, RK;Moore, JB;Cousins, RJ
哺乳动物的营养状况影响多种生理过程及其相关基因表达的稳态平衡。虽然DNA阵列分析可以监测大量的基因，有没有在一个完整的动物系统中的微量营养素缺乏症的表达谱的报告。在这份报告中，我们已经测试了使用cDNA阵列来比较啮齿动物锌缺乏早期阶段已知功能基因表达的整体变化的可行性。通过实时定量PCR测量金属硫蛋白1、锌转运蛋白2和uroguarylin的mRNA水平改变，证明了这种缺陷的基因调节作用，所有这些基因以前都被记录为锌调节基因。由于该模型系统内的低水平固有噪声和最近报道的用于微阵列统计分析的统计工具的应用[Tusher，V.G.，蒂布希拉尼河& Chu，G.等人（2001）Proc. Acad. Sci. USA 98，5116-5121]，我们证明了可重复地鉴定由这种单一微量营养素缺乏产生的mRNA丰度的适度变化的能力。在通过该阵列图谱鉴定的基因中，有影响信号传导途径、生长、转录、氧化还原和能量利用的肠道基因。此外，通过实时定量PCR证实了日粮锌供应对这些基因表达的影响。总体而言，这些数据支持cDNA阵列表达谱的有效性，以调查特定营养素的多效性效应，并可能提供一种方法来建立标志物，用于评估营养状况。
Mammalian nutritional status affects the homeostatic balance of multiple physiological processes and their associated gene expression. Although DNA array analysis can monitor large numbers of genes, there are no reports of expression profiling of a micronutrient deficiency in an intact animal system. in this report, we have tested the feasibility of using cDNA arrays to compare the global changes in expression of genes of known function that occur in the early stages of rodent zinc deficiency. The gene-modulating effects of this deficiency were demonstrated by real-time quantitative PCR measurements of altered mRNA levels for metallothionein 1, zinc transporter 2, and uroguarylin, all of which have been previously documented as zinc-regulated genes. As a result of the low level of inherent noise within this model system and application of a recently reported statistical tool for statistical analysis of microarrays [Tusher, V.G., Tibshirani, R. & Chu, G. (2001) Proc. Natl. Acad. Sci. USA 98, 5116-5121], we demonstrate the ability to reproducibly identify the modest changes in mRNA abundance produced by this single micronutrient deficiency. Among the genes identified by this array profile are intestinal genes that influence signaling pathways, growth, transcription, redox, and energy utilization. Additionally, the Influence of dietary zinc supply on the expression of some of these genes was confirmed by real-time quantitative PCR. Overall, these data support the effectiveness of cDNA array expression profiling to investigate the pleiotropic effects of specific nutrients and may provide an approach to establishing markers for assessment of nutritional status.