Sqstm1-KO 基因敲除小鼠

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产品名称

Sqstm1-KO 基因敲除小鼠

产品编号

S-KO-03528

品系全称

C57BL/6JCya-Sqstm1em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-18412-Sqstm1-B6J-VA

品系状态

使用本品系发表的文献需注明: Sqstm1-KO 基因敲除小鼠 mice (Strain S-KO-03528) 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
sequestosome 1
基因别称
A170,OSF-6,Osi,STAP,STONE14,p62
染色体号
Chr 11 (Mouse)
转录本 ID
NCBI: NM_011018 | Ensembl: ENSMUST00000102774
修饰方式
全身性基因敲除
靶向范围
Exon 2~8
敲除长度
~7.1 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:107931Mice homozygous for one knock-out allele exhibit impaired osteoclastogenesis in response to osteoclastogenic factors. Mice homozygous and heterozygous for a knock-in allele exhibit osteolytic lesion with increased bone formation, mineral apposition rate,and osteoclast numbers. Heterozygosity for the hyperactivating p.S351E mutation leads to hyperkeratosis in stomach and esophagus and, consequently, malnutrition, dehydration and severe growth retardation.
SQSTM1,也称为p62或Sequestosome 1,是一种重要的自噬受体蛋白。它通过识别和招募泛素化的底物到自噬体中,在自噬过程中发挥关键作用。SQSTM1还与多种神经退行性疾病有关,包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症(ALS)[1]。

SQSTM1在细胞应激反应中也发挥重要作用,例如在氧化应激条件下,它通过激活Nrf2信号通路来促进细胞抗氧化能力[2]。此外,SQSTM1还参与调节细胞凋亡和炎症反应[3]。

在遗传性疾病中,SQSTM1基因的突变与多种疾病的发生发展相关。例如,SQSTM1基因的突变与Paget病、动脉粥样硬化性脑梗死和肌萎缩侧索硬化症(ALS)的表型异质性有关[4][5][6]。这些研究表明,SQSTM1基因的突变可能导致自噬功能障碍,进而影响疾病的发生发展。

在糖尿病皮肤中,SQSTM1的表达下调,导致自噬通量受损,影响伤口愈合[7]。在ALS和额颞叶痴呆(FTLD)中,SQSTM1的突变导致选择性自噬和Nrf2抗氧化应激途径受损,引起神经毒性[8]。此外,SQSTM1基因的变异还与前列腺癌的发病机制相关[9]。这些研究揭示了SQSTM1在多种疾病中的作用,为进一步研究疾病的发生机制和治疗提供了新的思路。

综上所述,SQSTM1是一种重要的自噬受体蛋白,参与调控细胞应激反应和疾病的发生发展。SQSTM1基因的突变与多种疾病相关,包括Paget病、动脉粥样硬化性脑梗死、ALS、糖尿病皮肤病变和前列腺癌。深入研究SQSTM1的功能和作用机制,有助于揭示疾病的发生机制,为疾病的诊断和治疗提供新的思路和策略。

参考文献:
1. Almeida, Maria Rosário, Silva, Ana Rita, Elias, Inês, Galego, Orlando, Santo, Gustavo Cordeiro. 2020. SQSTM1 gene as a potential genetic modifier of CADASIL phenotype. In Journal of neurology, 268, 1453-1460. doi:10.1007/s00415-020-10308-5. https://pubmed.ncbi.nlm.nih.gov/33216222/
2. Liang, Diefei, Lin, Wei-Jye, Ren, Meng, Yan, Li, Wang, Wei. 2021. m6A reader YTHDC1 modulates autophagy by targeting SQSTM1 in diabetic skin. In Autophagy, 18, 1318-1337. doi:10.1080/15548627.2021.1974175. https://pubmed.ncbi.nlm.nih.gov/34657574/
3. Deng, Zhiqiang, Lim, Junghyun, Wang, Qian, Chen, Shi, Yue, Zhenyu. 2019. ALS-FTLD-linked mutations of SQSTM1/p62 disrupt selective autophagy and NFE2L2/NRF2 anti-oxidative stress pathway. In Autophagy, 16, 917-931. doi:10.1080/15548627.2019.1644076. https://pubmed.ncbi.nlm.nih.gov/31362587/
4. Chen, Ruo-Yang, Li, Da-Wei, Xie, Hui, Zhang, Wei-Jie, Hou, Jian-Quan. 2023. Gene signature and prediction model of the mitophagy-associated immune microenvironment in renal ischemia-reperfusion injury. In Frontiers in immunology, 14, 1117297. doi:10.3389/fimmu.2023.1117297. https://pubmed.ncbi.nlm.nih.gov/37056767/
5. Zhou, Lingli, He, Xing, Wang, Liqiu, Zeng, Huasong, Cui, Jun. 2022. Palmitoylation restricts SQSTM1/p62-mediated autophagic degradation of NOD2 to modulate inflammation. In Cell death and differentiation, 29, 1541-1551. doi:10.1038/s41418-022-00942-z. https://pubmed.ncbi.nlm.nih.gov/35066577/
6. Shi, Qing, Jin, Xiaofeng, Zhang, Pingzhao, Gao, Kun, Wang, Chenji. 2022. SPOP mutations promote p62/SQSTM1-dependent autophagy and Nrf2 activation in prostate cancer. In Cell death and differentiation, 29, 1228-1239. doi:10.1038/s41418-021-00913-w. https://pubmed.ncbi.nlm.nih.gov/34987184/
7. Peng, Shuang-Zhou, Chen, Xiao-Hui, Chen, Si-Jie, Su, Ying, Zhang, Xiao-Kun. 2021. Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates. In Nature communications, 12, 5989. doi:10.1038/s41467-021-26295-8. https://pubmed.ncbi.nlm.nih.gov/34645818/
8. Donáth, Judit, Balla, Bernadett, Pálinkás, Márton, Ralston, Stuart H, Poór, Gyula. 2020. Pattern of SQSTM1 Gene Variants in a Hungarian Cohort of Paget's Disease of Bone. In Calcified tissue international, 108, 159-164. doi:10.1007/s00223-020-00758-4. https://pubmed.ncbi.nlm.nih.gov/32978683/
9. Xie, Weihong, Tian, Shuo, Yang, Jiahui, Ji, Yanqin, Cui, Jun. 2022. OTUD7B deubiquitinates SQSTM1/p62 and promotes IRF3 degradation to regulate antiviral immunity. In Autophagy, 18, 2288-2302. doi:10.1080/15548627.2022.2026098. https://pubmed.ncbi.nlm.nih.gov/35100065/