Expression profiling of Notch constitutive activation in the liver of mice

Notch intracellular domain (NICD) is the active form of the Notch receptor. In this mouse model, NICD is inserted in the Rosa26 locus downstream of a loxP-STOP-LoxP (lsl) sequence and therefore NICD expression is dependant on Cre recombinase expression (Mono transgenic control Rosa26-lsl-NICD) . These mice are crossed with the AFP-Cre strain that expresses Cre in hepatoblasts due to its regulation by the AFP promoter and albumin enhancer (Double transgenic mutant AFP-Cre/Rosa26-lsl-NICD). Newborn mice at day 0 and day 2 are sacrificed and liver RNA samples from control monotransgenic Rosa26-lsl-NICD and from bitransgenic AFP-Cre/Rosa26-lsl-NICD (AFP-NICD) are obtained. Whole genome expression profiling of these samples is submitted. Five liver samples from Control mice and six liver samples from Mutant mice are analyzed using the Agilent Whole Mouse Genome Oligo Microarray G4122A platform. Array data was preprocessed and analyzed using GenePattern software and R.

Notch胞内结构域（Notch intracellular domain, NICD）是Notch受体的活性形式。在本小鼠模型中，NICD被插入至loxP-STOP-LoxP（lsl）序列下游的Rosa26基因座中，因此NICD的表达依赖于Cre重组酶的表达，即单转基因对照Rosa26-lsl-NICD小鼠。将该品系小鼠与AFP-Cre品系杂交，该品系因受甲胎蛋白（Alpha-fetoprotein, AFP）启动子与白蛋白增强子调控，可在肝母细胞中表达Cre重组酶，由此获得双转基因突变体AFP-Cre/Rosa26-lsl-NICD小鼠。对出生后第0天和第2天的新生小鼠实施安乐死后，分别采集单转基因对照Rosa26-lsl-NICD小鼠与双转基因AFP-Cre/Rosa26-lsl-NICD（简称AFP-NICD）小鼠的肝脏RNA样本。本研究对上述样本开展全基因组表达谱分析，相关数据已提交；采用安捷伦全小鼠基因组寡核苷酸微阵列G4122A平台，对5份对照小鼠肝脏样本与6份突变小鼠肝脏样本进行检测。芯片数据经GenePattern软件与R语言完成预处理与分析。