Functional connection between fetal brain development and longevity in mice

The objective of the present study is to investigate gene regulation in developing fetal brain in congenic or inbred mice strains that differ in longevity. Gene expression and alternative splice variants were analyzed in a genome-wide manner in the fetal brain of C57BL/6J mice (long-lived), and compared to that of a congenic strain (short-lived) or an inbred strain AKR/J (short-lived) on days 12, 15 and 17 of gestation. The analysis showed a contrasting gene expression pattern during fetal brain development in these mice. Genes related to brain development, aging and spliceosome were significantly differentially regulated in the fetal brain of the short-lived mice when brain developed from d15 to d17. A significantly reduced number of splice variants were observed on d15 compared to d12 or d17 but in a strain-dependent manner. RNA sequencing was performed with the fetal brain of C57BL/6J mice (long-lived), and compared to that of a congenic strain (short-lived) or an inbred strain AKR/J (short-lived) on days 12, 15 and 17 of gestation (three replicates per time point).本研究旨在探究寿命存在差异的同类系（congenic）或近交系（inbred）小鼠品系中，发育中胎儿大脑的基因调控机制。研究以C57BL/6J小鼠（长寿品系）的胎儿脑组织为对象，采用全基因组分析策略，对其基因表达与可变剪接变体进行检测，并分别与同系短寿小鼠品系、近交系AKR/J小鼠（短寿品系）在妊娠第12、15、17天的样本开展对比分析。分析结果显示，两类小鼠的胎儿大脑发育过程中基因表达模式存在显著差异。当胎儿大脑从妊娠第15天发育至第17天时，短寿小鼠胎儿脑组织中与大脑发育、衰老及剪接体（spliceosome）相关的基因呈现出显著的差异调控现象。相较于妊娠第12天或第17天，妊娠第15天的胎儿脑组织中可变剪接变体数量显著减少，但该变化呈现品系依赖性特征。本研究针对C57BL/6J小鼠（长寿品系）的胎儿脑组织实施RNA测序（RNA sequencing），并将其结果与同系短寿小鼠品系、近交系AKR/J小鼠（短寿品系）在妊娠第12、15、17天的样本进行对比，每个时间点设置3次生物学重复。