Transcription profiling by array of liver from Ercc1 knock-out mice

To investigate the cause of the premature aging features in the Ercc1-/- mouse, we compared the entire transcriptome of the Ercc1-/- mouse liver to that of wildtype littermates at the age of 15 days, when the Ercc1-/- mice reached their maximal weight and had symptoms of progeria, yet overall pathology was still limited. The liver was selected because the tissue showed several well-defined histological changes associated with aging (polyploidy and intranuclear inclusions) as well as evidence that it is responding to endogenous genotoxic stress (stabilized p53).为探究Ercc1-/-小鼠出现早衰表型的成因，本研究于小鼠出生后15日龄时，对Ercc1-/-小鼠肝脏与同窝野生型小鼠肝脏的全转录组（transcriptome）进行对比分析。该时间节点下，Ercc1-/-小鼠已达到体重峰值并表现出早衰症状，但整体病理学损伤仍较为局限。选择肝脏作为研究组织，是因其存在若干与衰老相关的明确组织学改变（包括多倍体化与核内包涵体），同时具备响应内源性遗传毒性应激的相关证据（即p53蛋白稳定化）。