RNA-seq of cerebellum from Eif2b5[R191H] mice

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 from 5-month-old homozygous Eif2b5[R191H] (n=4) and WT mice (n=5).整合应激反应（integrated stress response, ISR）是一类高度保守的信号通路，可被多种应激刺激所激活，涵盖内质网应激（ER stress）、线粒体应激、氨基酸剥夺及病毒感染等多种诱因。该通路的核心应激感受器与关键效应分子为eIF2B，其5个亚基中任意一个发生功能丧失突变，均可导致人类罹患脑白质消失症（Vanishing White Matter disease, VWM）。本研究构建并表征了携带不同致病突变的小鼠模型，旨在模拟VWM疾病，并解析慢性ISR激活对机体及细胞生理状态的影响。本研究针对5月龄纯合子Eif2b5[R191H]小鼠（n=4）与野生型（WT）小鼠（n=5）的小脑组织开展了批量RNA测序（bulk RNA-seq）。