The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
BMC Genomics. 2011 Mar 30;12:167. doi: 10.1186/1471-2164-12-167.
Transcripts can exhibit significant variation in tissue samples from inbred laboratory mice. We have designed and carried out a microarray experiment to examine transcript variation across samples from adipose, heart, kidney, and liver tissues of C57BL/6J mice and to partition variation into within-mouse and between-mouse components. Within-mouse variance captures variation due to heterogeneity of gene expression within tissues, RNA-extraction, and array processing. Between-mouse variance reflects differences in transcript abundance between genetically identical mice.
The nature and extent of transcript variation differs across tissues. Adipose has the largest total variance and the largest within-mouse variance. Liver has the smallest total variance, but it has the most between-mouse variance. Genes with high variability can be classified into groups with correlated patterns of expression that are enriched for specific biological functions. Variation between mice is associated with circadian rhythm, growth hormone signaling, immune response, androgen regulation, lipid metabolism, and the extracellular matrix. Genes showing correlated patterns of within-mouse variation are also associated with biological functions that largely reflect heterogeneity of cell types within tissues.
Genetically identical mice can experience different individual outcomes for medically important traits. Variation in gene expression observed between genetically identical mice can identify functional classes of genes that are likely to vary in the absence of experimental perturbations, can inform experimental design decisions, and provides a baseline for the interpretation of gene expression data in interventional studies. The extent of transcript variation among genetically identical mice underscores the importance of stochastic and micro-environmental factors and their phenotypic consequences.
同窝系实验室小鼠的组织样本中转录本存在显著差异。我们设计并进行了一项微阵列实验，以研究 C57BL/6J 小鼠的脂肪、心脏、肾脏和肝脏组织样本中转录本的变化，并将变化分为小鼠内和小鼠间成分。小鼠内方差捕获了由于组织内基因表达、RNA 提取和芯片处理的异质性引起的变化。小鼠间方差反映了遗传上相同的小鼠之间转录物丰度的差异。
转录本变化的性质和程度在不同组织之间存在差异。脂肪的总方差和小鼠内方差最大。肝脏的总方差最小，但小鼠间方差最大。具有高变异性的基因可以分为具有相关表达模式的组，这些组富含特定的生物学功能。小鼠间的变异与昼夜节律、生长激素信号、免疫反应、雄激素调节、脂质代谢和细胞外基质有关。显示小鼠内变化相关模式的基因也与生物学功能相关，这些功能主要反映了组织内细胞类型的异质性。
遗传上相同的小鼠可能会经历对医学重要性状的不同个体结果。在遗传上相同的小鼠之间观察到的基因表达变化可以确定功能类别的基因，这些基因在没有实验干扰的情况下可能会发生变化，为实验设计决策提供信息，并为干预研究中基因表达数据的解释提供基线。遗传上相同的小鼠之间转录本变化的程度强调了随机和微环境因素及其表型后果的重要性。
