Microarray expression profiling of the Igf2 pathway dependency of Trp53 developmental and tumour phenotypes in mice

We tested whether loss of p53 function leads to insulin-like growth factor 2 (IGF2) pathway dependency in vivo in genetically defined mouse models. Unexpectedly we found lethality, due to post-natal lung haemorrhage, occurred in Igf2 paternal null allele female mice (Igf2-p) but only if derived from double heterozygote fathers (Igf2-p, p53+/-). Consequently we investigated the effects of paternal genotype (wild-type, Igf2-p and Igf2-p, p53+/-) on gene expression. Microarray gene expression profiling of whole mouse embryos (embryonic day 9.5) revealed that lethality was associated with a specific gene signature. Since double heterozygote female offspring (Igf2-p, p53+/-) of Igf2-p, p53+/- fathers did not have the lethality phenotype we identified gene expression changes associated with this 'rescue'. Supplementary information available when browsing all available files.本研究在遗传背景明确的小鼠模型中，探究了p53功能缺失是否会在体内引发胰岛素样生长因子2（IGF2）通路依赖现象。出人意料的是，我们观察到携带Igf2父系缺失等位基因的雌性小鼠（Igf2-p）可因产后肺出血死亡，且该致死表型仅在其亲本为双杂合子父鼠（Igf2-p, p53+/-）时才会出现。基于上述发现，我们进一步探究了父本基因型（野生型、Igf2-p及Igf2-p, p53+/-）对基因表达的影响。对胚胎发育第9.5天的完整小鼠胚胎进行微阵列基因表达谱分析后发现，该致死表型与特定的基因表达特征显著相关。由于Igf2-p, p53+/-父鼠所产下的双杂合子雌性后代（Igf2-p, p53+/-）并未表现出致死表型，我们进一步鉴定出了与该"表型挽救"现象相关的基因表达变化。所有相关补充信息均可通过浏览全部可用文件获取。