RNA-seq of mouse embryonic fibroblasts from Eif2b1[N208Y] mice cultured with or without 2BAct

The integrated stress response (ISR) is a conserved signaling pathway triggered by a variety of insults that include ER stress, mitochondrial stress, amino acid deprivation, and viral infection. The essential stress sensor and key effector of this pathway is eIF2B, and loss-of-function mutations in any of its 5 subunits can lead to Vanishing White Matter disease (VWM) in humans. We generated and characterized mouse models harboring different pathogenic mutations to model VWM and to understand the impact of chronic ISR activation. Here, we performed bulk RNA-seq on mouse embryonic fibroblasts (MEFs) isolated from homozygous Eif2b1[N208Y] and WT mouse embryos. MEFs were cultured in 200 nM small molecule eIF2B activator 2BAct, then washed and either maintained in 200 nM 2BAct or switched to 2BAct-withdrawn media (0 nM) to induce an acute ISR.