Effect of neuron-specific spliced XBP1 (XBP1s) overexpression on gene expression in the mouse brain

One major component of cellular proteome resides in the endoplasmic reticulum (ER), the key organelle for protein biogenesis in the secretory pathway. Disruption of ER proteostasis leads to ER stress, which subsequently activates multiple adaptive stress response pathways, collectedly termed as the unfolded protein response (UPR). One UPR branch is mediated by IRE1(inositol-requiring enzyme 1). Activation of the IRE1 UPR branch generates a potent transcriptional factor: spliced X-box–binding protein-1 (XBP1s). Since activation of this UPR branch has been shown to be neuroprotective in brain ischemia/stroke, it is critical to identify the XBP1s-regulated genes in neurons in vivo and thus help determine the molecular mechanisms underlying the beneficial effects exerted by this UPR branch. In this study, we performed RNA-Seq analysis on the hippocampus from XBP1s conditional transgenic mice. Overall design: Compare gene expression between control mice and XBP1s conditional transgenic (TRE-XBP1s;Camk2a-tTA ) mice (n = 4).