Constitutive expression of spliced XBP1 causes perinatal lethality in mice.
Constitutive expression of spliced XBP1 causes perinatal lethality in mice.
复制标题
拼接XBP 1的组成性表达导致小鼠围产期死亡。
DOI：
10.1002/dvg.23420
复制
发表时间：
2021-06
期刊：
影响因子：
1.5
通讯作者：
Lu, Yongbo
中科院分区：
文献类型：
--
作者：
Xu, Qian;Zhang, Hua;Wang, Suzhen;Qin, Chunlin;Lu, Yongbo
在内质网（ER）应激时，肌醇需要酶1（IRE 1）被激活并催化未剪接的X-box结合蛋白1（XBP 1U）mRNA的非常规剪接，以产生编码有效的XBP 1 S转录因子的剪接的XBP 1（XBP 1 S）mRNA。XBP 1 S是IRE 1分支的关键介质，其对于缓解ER应激是必需的。我们产生了一种新的小鼠品系（称为“Xbp 1CS/+”小鼠），其在Cre重组酶介导的重组后组成型表达XBP 1 S。这些小鼠与Twist 2 Cre重组酶（Twist 2-Cre）敲入小鼠的进一步育种产生Twist 2-Cre; Xbp 1CS/+小鼠。大多数Twist 2-Cre; Xbp 1CS/+小鼠在出生后不久死亡。逆转录聚合酶链反应（RT-PCR）显示，XBP 1 S的组成型表达发生在各种小鼠组织检查，但不是在大脑中。免疫组织化学证实，尽管在Twist 2-Cre; Xbp 1CS/+和对照小鼠的颅骨中发现了总XBP 1（XBP 1U和XBP 1 S）的免疫染色信号，但仅在Twist 2-Cre; Xbp 1CS/+小鼠中检测到XBP 1 S的信号，而在对照小鼠中未检测到。这些结果表明，精确控制XBP 1 S的产生对小鼠的正常发育至关重要。
Upon endoplasmic reticulum (ER) stress, inositol-requiring enzyme 1 (IRE1) is activated and catalyzes a 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 “Xbp1CS/+” 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;Xbp1CS/+ mice. Most Twist2-Cre;Xbp1CS/+ 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;Xbp1CS/+ and control mice, the signals for XBP1S were only detected in the Twist2-Cre;Xbp1CS/+ mice, but not in the control mice. These results suggest that a precise control of XBP1S production is essential for normal mouse development.
登录
查看更多内容
影响因子：
64.5
作者：
Liu J;Ibi D;Taniguchi K;Lee J;Herrema H;Akosman B;Mucka P;Salazar Hernandez MA;Uyar MF;Park SW;Karin M;Ozcan U
通讯作者：
Ozcan U
影响因子：
7.8
作者：
Kimata, Yukio;Ishiwata-Kimata, Yuki;Ito, Tatsuhiko;Hirata, Aiko;Suzuki, Tomohide;Oikawa, Daisuke;Takeuchi, Masato;Kohno, Kenji
通讯作者：
Kohno, Kenji
影响因子：
11.4
作者：
Lee, AH;Chu, GC;Glimcher, LH
通讯作者：
Glimcher, LH
影响因子：
82.9
作者：
Iwawaki, T;Akai, R;Miura, M
通讯作者：
Miura, M
影响因子：
64.5
作者：
Lee, Kenneth P. K.;Dey, Madhusudan;Sicheri, Frank
通讯作者：
Sicheri, Frank