RNA-seq of cerebellum, kidney, liver, lung, muscle, spinal cord, and spleen from Eif2b1[N208Y] mice with or without 2BAct treatment

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 on organismal and cellular physiology. Here, we performed bulk RNA-seq on the cerebellum, kidney, liver, lung, muscle, spinal cord, and spleen from 4-month-old homozygous Eif2b1[N208Y] and WT mice, either maintained on a 30 mg/kg 2BAct diet or withdrawn from the diet for 3 days. 2BAct is a small molecule eIF2B activator that can stabilize eIF2B and improve its function. This study also includes WT control mice naive to 2BAct diet.