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).