Eif2ak3-KO 基因敲除小鼠

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产品名称

Eif2ak3-KO 基因敲除小鼠

产品编号

S-KO-16093

品系全称

C57BL/6JCya-Eif2ak3em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-13666-Eif2ak3-B6J-VA

品系状态

使用本品系发表的文献需注明: Eif2ak3-KO 基因敲除小鼠 mice (Strain S-KO-16093) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量

基本信息

基因研究概述

质控标准

基因
基因全称
eukaryotic translation initiation factor 2 alpha kinase 3
基因别称
Pek,Perk
染色体号
Chr 6 (Mouse)
转录本 ID
NCBI: NM_010121 | Ensembl: ENSMUST00000034093
修饰方式
全身性基因敲除
靶向范围
Exon 2
敲除长度
~1.3 kb
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
MGI:1341830Homozygous mutant mice develop exocrine pancreatic insufficiency and progressive diabetes mellitus. They are growth retarded, hyperglycemic, exhibit increased cell death in the pancreas, have decreased numbers of pancreatic beta cells and about half diebefore weaning.
Eif2ak3,也称为PERK(PKR-like ER kinase),是一种内质网(ER)定位的激酶,属于eIF2α激酶家族。它的主要功能是在内质网应激(ERS)条件下调节蛋白质翻译,参与未折叠蛋白反应(UPR)。Eif2ak3通过磷酸化真核翻译起始因子2α(eIF2α)的第51位丝氨酸残基,抑制蛋白质合成,从而减轻内质网负荷,保护细胞免受应激损伤[9]。Eif2ak3在多种生物学过程中发挥重要作用,包括细胞凋亡、自噬、炎症反应和细胞代谢等。

Eif2ak3在内质网应激条件下被激活,参与调节细胞凋亡和自噬。在肝脏炎症中,Eif2ak3的激活可以促进细胞凋亡,加剧肝损伤[1]。然而,在肠上皮细胞中,Eif2ak3的激活可以促进自噬,维持肠道屏障功能[2]。在骨关节炎的进展过程中,Eif2ak3的激活可以促进细胞凋亡,导致软骨退化[3]。此外,Eif2ak3还与细胞衰老和器官纤维化相关,其激活可以促进细胞衰老和器官纤维化[4]。

Eif2ak3在肿瘤进展中也发挥重要作用。在内质网应激条件下,Eif2ak3的激活可以促进肿瘤细胞凋亡,抑制肿瘤生长[5]。然而,在缺氧条件下,Eif2ak3的激活可以促进肿瘤细胞自噬,帮助肿瘤细胞适应缺氧环境,促进肿瘤生长[6]。此外,Eif2ak3的基因突变还与某些类型的糖尿病相关,例如Wolcott-Rallison综合征和1型糖尿病[7,8]。

Eif2ak3的研究对于深入理解内质网应激的调控机制和疾病发生机制具有重要意义。通过靶向Eif2ak3的激活或抑制,可以调节细胞凋亡、自噬和炎症反应,为治疗多种疾病提供新的思路和策略。

参考文献:
1. Brenner, Catherine, Galluzzi, Lorenzo, Kepp, Oliver, Kroemer, Guido. 2013. Decoding cell death signals in liver inflammation. In Journal of hepatology, 59, 583-94. doi:10.1016/j.jhep.2013.03.033. https://pubmed.ncbi.nlm.nih.gov/23567086/
2. Foerster, Elisabeth G, Mukherjee, Tapas, Cabral-Fernandes, Liliane, Girardin, Stephen E, Philpott, Dana J. 2021. How autophagy controls the intestinal epithelial barrier. In Autophagy, 18, 86-103. doi:10.1080/15548627.2021.1909406. https://pubmed.ncbi.nlm.nih.gov/33906557/
3. Yang, Hongxu, Wen, Yi, Zhang, Mian, Xiao, Guozhi, Wang, Meiqing. 2019. MTORC1 coordinates the autophagy and apoptosis signaling in articular chondrocytes in osteoarthritic temporomandibular joint. In Autophagy, 16, 271-288. doi:10.1080/15548627.2019.1606647. https://pubmed.ncbi.nlm.nih.gov/31007149/
4. Zhang, Dan, Liu, Yutong, Zhu, Yezhang, Shen, Li, Xu, Pinglong. 2022. A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis. In Nature cell biology, 24, 766-782. doi:10.1038/s41556-022-00894-z. https://pubmed.ncbi.nlm.nih.gov/35501370/
5. Rozpedek, W, Pytel, D, Mucha, B, Diehl, J A, Majsterek, I. . The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress. In Current molecular medicine, 16, 533-44. doi:. https://pubmed.ncbi.nlm.nih.gov/27211800/
6. Cui, Kun, Li, Zhizheng. 2023. Identification and analysis of type 2 diabetes-mellitus-associated autophagy-related genes. In Frontiers in endocrinology, 14, 1164112. doi:10.3389/fendo.2023.1164112. https://pubmed.ncbi.nlm.nih.gov/37223013/
7. Allotey, R A, Mohan, V, McDermott, M F, Froguel, P, Hitman, G A. . The EIF2AK3 gene region and type I diabetes in subjects from South India. In Genes and immunity, 5, 648-52. doi:. https://pubmed.ncbi.nlm.nih.gov/15483661/
8. Gürbüz, Fatih, Yüksel, Bilgin, Topaloğlu, Ali Kemal. 2016. Wolcott-Rallison Syndrome with Novel EIF2AK3 Gene Mutation. In Journal of clinical research in pediatric endocrinology, 8, 496-497. doi:10.4274/jcrpe.3065. https://pubmed.ncbi.nlm.nih.gov/27145240/
9. Kennedy, Donna, Samali, Afshin, Jäger, Richard. . Methods for studying ER stress and UPR markers in human cells. In Methods in molecular biology (Clifton, N.J.), 1292, 3-18. doi:10.1007/978-1-4939-2522-3_1. https://pubmed.ncbi.nlm.nih.gov/25804744/