Upon endoplasmic reticulum (ER) stress, inositol-requiring enzyme 1 (IRE1) is activated and catalyzes nonconventional splicing of an unspliced X-box binding protein 1 (XBP1U) mRNA to yield a spliced XBP1 (XBP1S) mRNA that encodes a potent XBP1S transcription factor. XBP1S is a key mediator of the IRE1 branch that is essential for alleviating ER stress. We generated a novel mouse strain (referred to as “Xbp1^CS/+” mice) that constitutively expressed XBP1S after Cre recombinase-mediated recombination. Further breeding of these mice with Twist2 Cre recombinase (Twist2-Cre) knock-in mice generated Twist2-Cre;Xbp1^CS/+ mice. Most Twist2-Cre;Xbp1^CS/+ mice died shortly after birth. Reverse-transcription polymerase chain reaction (RT-PCR) showed that constitutive expression of XBP1S occurred in various mouse tissues examined, but not in the brain. Immunohistochemistry confirmed that although the immunostaining signals for total XBP1 (XBP1U and XBP1S) were found in the calvarial bones in both Twist2-Cre;Xbp1^CS/+ and control mice, the signals for XBP1S were only detected in the Twist2-Cre;Xbp1^CS/+ mice, but not in the control mice. These results suggest that a precise control of XBP1S production is essential for normal mouse development.

中文翻译：

---

剪接 XBP1 的组成型表达导致小鼠围产期致死率

在内质网 (ER) 应激时，肌醇需要酶 1 (IRE1) 被激活并催化未剪接的 X-box 结合蛋白 1 (XBP1U) mRNA 的非常规剪接，以产生编码有效 XBP1S 转录的剪接 XBP1 (XBP1S) mRNA因素。XBP1S 是 IRE1 分支的关键介质，对于缓解 ER 压力至关重要。我们产生了一种新的小鼠品系（称为“ Xbp1 ^CS/+ ”小鼠），它在 Cre 重组酶介导的重组后组成型表达 XBP1S。这些小鼠与Twist2 Cre 重组酶 ( Twist2-Cre ) 敲入小鼠的进一步繁殖产生了Twist2-Cre；Xbp1 ^CS/+小鼠。大多数Twist2-Cre ; Xbp1^CS/+小鼠在出生后不久死亡。逆转录聚合酶链反应 (RT-PCR) 表明 XBP1S 的组成型表达发生在所检查的各种小鼠组织中，但不在大脑中。免疫组织化学证实，尽管在 Twist2 -Cre的颅骨中发现了总 XBP1（XBP1U 和 XBP1S）的免疫染色信号；Xbp1 ^CS/+和对照小鼠，仅在 Twist2 -Cre中检测到 XBP1S 的信号；Xbp1 ^CS/+小鼠，但在对照小鼠中没有。这些结果表明，精确控制 XBP1S 的产生对于正常的小鼠发育至关重要。