Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, Texas, USA.
Genesis. 2021 Jun;59(5-6):e23420. doi: 10.1002/dvg.23420. Epub 2021 Apr 23.
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 " 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 mice. Most Twist2-Cre;Xbp1 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 and control mice, the signals for XBP1S were only detected in the Twist2-Cre;Xbp1 mice, but not in the control mice. These results suggest that a precise control of XBP1S production is essential for normal mouse development.
在内质网（ER）应激时，肌醇需求酶 1（IRE1）被激活并催化未剪接的 X 盒结合蛋白 1（XBP1U）mRNA 的非常规剪接，产生剪接的 XBP1（XBP1S）mRNA，其编码有效的 XBP1S 转录因子。XBP1S 是 IRE1 分支的关键介质，对于缓解 ER 应激至关重要。我们生成了一种新型小鼠品系（称为“Xbp1”小鼠），在 Cre 重组酶介导的重组后，该品系持续表达 XBP1S。将这些小鼠与 Twist2 Cre 重组酶（Twist2-Cre）敲入小鼠进一步繁殖，生成了 Twist2-Cre；Xbp1 小鼠。大多数 Twist2-Cre；Xbp1 小鼠在出生后不久就死亡。逆转录聚合酶链反应（RT-PCR）显示，XBP1S 的组成型表达发生在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 Twist2-Cre；Xbp1 和对照小鼠的颅骨骨中均发现了总 XBP1（XBP1U 和 XBP1S）的免疫染色信号，但 XBP1S 的信号仅在 Twist2-Cre；Xbp1 小鼠中检测到，而在对照小鼠中未检测到。这些结果表明，XBP1S 产生的精确控制对于正常的小鼠发育至关重要。
