Transcription profiling by array of fetal hearts from mice mutant for ERRgamma

3 ventricles from E18.5 male mice were pooled for each array. Three arrays per genotype. Title: ERRgamma Directs and Maintains the Transition to Oxidative Metabolism in the Post-Natal Heart; Abstract: At birth the heart undergoes a critical metabolic switch to transition from a predominant dependence on carbohydrates during fetal life to a greater dependence on postnatal oxidative metabolism. This remains the principle metabolic state throughout life; although pathologic conditions such as heart failure and cardiac hypertrophy reactivate components of the fetal genetic program to increase carbohydrate utilization. Disruption of the ERRγ gene, which is expressed at high levels in the fetal and postnatal mouse heart, blocks this switch resulting in lactatemia, electrocardiographic (ECG) abnormalities and death during the first week of life. Genomic ChIP-on-chip and expression analysis at E18.5 clearly identifies ERRγ as both a direct and indirect regulator of a nuclear-encoded mitochondrial genetic network that coordinates the postnatal metabolic transition. These findings reveal an unexpected and essential molecular genetic component of the oxidative metabolic gene program in the heart and highlight ERRgamma in the study of cardiac hypertrophy and failure. Experiment Overall Design: Fetal mice were collected by caesarean secation. Hearts were stored in RNALater (Qiagen)每个基因芯片阵列（array）采用3只胎龄E18.5的雄性小鼠心室组织混合制备；每个基因型设置3张基因芯片阵列。 标题：雌激素相关受体γ（ERRgamma）调控并维持出生后心脏向氧化代谢的转变 摘要：心脏在出生时会经历关键的代谢转换：从胎儿期以碳水化合物为主要能量依赖来源，转变为出生后更依赖氧化代谢的状态，这一代谢模式将贯穿终生；尽管心力衰竭、心肌肥厚等病理状态会重新激活胎儿期基因程序的部分组分，以提升碳水化合物的利用效率。在胎鼠及出生后小鼠心脏中高表达的ERRgamma基因被敲除后，会阻断上述代谢转换过程，进而引发乳酸性酸中毒、心电图（ECG）异常，并导致小鼠在出生后第一周内死亡。在E18.5胎龄小鼠中开展的全基因组染色质免疫沉淀芯片（ChIP-on-chip）与表达谱分析明确证实，ERRgamma可作为直接与间接调控因子，参与协调出生后代谢转换的核编码线粒体基因网络的调控过程。本研究结果揭示了心脏氧化代谢基因程序中此前未被发现的关键分子遗传组分，并凸显了ERRgamma在心肌肥厚与心力衰竭研究中的重要意义。 实验总体设计：通过剖腹产术采集胎鼠心脏组织，样本保存于Qiagen公司的RNALater试剂中。