Nudt1-KO 基因敲除小鼠

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产品名称

Nudt1-KO 基因敲除小鼠

产品编号

S-KO-20212

品系全称

C57BL/6JCya-Nudt1em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-17766-Nudt1-B6J-VB

品系状态

使用本品系发表的文献需注明: Nudt1-KO 基因敲除小鼠 mice (Strain S-KO-20212) 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
nudix hydrolase 1
基因别称
Mth1
染色体号
Chr 5 (Mouse)
转录本 ID
NCBI: NM_008637 | Ensembl: ENSMUST00000050205
修饰方式
全身性基因敲除
靶向范围
Exon 3~4
敲除长度
~2.4 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:109280Aging mice homozygous for a knock-out allele show increased incidence of tumor formation in the lung, liver and stomach.
Nudt1,也称为MTH1(MutT homolog 1),是一种重要的Nudix水解酶。Nudix水解酶是一种广泛存在于生物体内的水解酶家族,负责催化Nudix框(nucleoside diphosphate-linked moiety X-type motif)序列的底物水解反应。Nudt1主要功能是催化氧化型DNA前体8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP)的水解,防止其被DNA聚合酶掺入DNA链中,从而保护细胞免受8-oxo-dGTP诱导的点突变。Nudt1的表达和活性与多种癌症的发生发展密切相关,被认为是许多类型人类癌症的普遍标志物。

在原发性胆管炎(PBC)中,Nudt1的表达与CD103+ TRM细胞(CD69+CD103+CD8+细胞)的积累和存活密切相关。Nudt1的阻断可以抑制CD103+ TRM细胞的细胞毒性效应,而Nudt1的过表达可以促进CD8+ T细胞的组织定植编程[1]。此外,Nudt1在胶质瘤、口腔鳞状细胞癌、肝细胞癌、肾细胞癌和结直肠癌等多种癌症中均表现出过表达,且与患者的预后密切相关[2,3,4,5,6,7,8,9,10]。

Nudt1在肿瘤发生发展中的作用机制包括:1)Nudt1通过调节DNA损伤修复相关基因的表达影响肿瘤细胞的DNA损伤修复能力;2)Nudt1通过影响氧化应激反应相关基因的表达影响肿瘤细胞的氧化应激反应;3)Nudt1通过影响免疫细胞浸润相关基因的表达影响肿瘤微环境的免疫状态;4)Nudt1通过影响细胞周期、细胞增殖、细胞迁移和细胞侵袭相关基因的表达影响肿瘤细胞的生物学行为。

综上所述,Nudt1是一种重要的Nudix水解酶,在肿瘤发生发展中发挥重要作用。Nudt1的表达和活性与多种癌症的发生发展密切相关,被认为是许多类型人类癌症的普遍标志物。Nudt1在肿瘤发生发展中的作用机制包括:1)Nudt1通过调节DNA损伤修复相关基因的表达影响肿瘤细胞的DNA损伤修复能力;2)Nudt1通过影响氧化应激反应相关基因的表达影响肿瘤细胞的氧化应激反应;3)Nudt1通过影响免疫细胞浸润相关基因的表达影响肿瘤微环境的免疫状态;4)Nudt1通过影响细胞周期、细胞增殖、细胞迁移和细胞侵袭相关基因的表达影响肿瘤细胞的生物学行为。

参考文献:
1. Huang, Bingyuan, Lyu, Zhuwan, Qian, Qiwei, You, Zhengrui, Ma, Xiong. 2022. NUDT1 promotes the accumulation and longevity of CD103+ TRM cells in primary biliary cholangitis. In Journal of hepatology, 77, 1311-1324. doi:10.1016/j.jhep.2022.06.014. https://pubmed.ncbi.nlm.nih.gov/35753523/
2. Ye, Minhui, Fang, Yingzhe, Chen, Lu, Jiang, Baishan, Qing, Guoliang. 2024. Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability. In Nature communications, 15, 2377. doi:10.1038/s41467-024-46572-6. https://pubmed.ncbi.nlm.nih.gov/38493213/
3. Wu, Yaqiu, Liu, Ling, Huang, Da, Wang, Qi, You, Chao. . Uncover DNA damage and repair-related gene signature and risk score model for glioma. In Annals of medicine, 55, 2200033. doi:10.1080/07853890.2023.2200033. https://pubmed.ncbi.nlm.nih.gov/37086071/
4. Shen, Yuchen, Zhang, Lei, Piao, Songlin, Li, Jichen, Saiyin, Wuliji. 2019. NUDT1: A potential independent predictor for the prognosis of patients with oral squamous cell carcinoma. In Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 49, 210-218. doi:10.1111/jop.12974. https://pubmed.ncbi.nlm.nih.gov/31732994/
5. Bialkowski, Karol, Kasprzak, Kazimierz S. 2019. A profile of 8-oxo-dGTPase activities in the NCI-60 human cancer panel: Meta-analytic insight into the regulation and role of MTH1 (NUDT1) gene expression in carcinogenesis. In Free radical biology & medicine, 148, 1-21. doi:10.1016/j.freeradbiomed.2019.12.036. https://pubmed.ncbi.nlm.nih.gov/31883466/
6. Ou, Qifeng, Ma, Ning, Yu, Zheng, Su, Qiao, Huang, Xiaohui. 2020. Nudix hydrolase 1 is a prognostic biomarker in hepatocellular carcinoma. In Aging, 12, 7363-7379. doi:10.18632/aging.103083. https://pubmed.ncbi.nlm.nih.gov/32341205/
7. Lin, Yongshuai, Zhang, Facai, Jin, Yinling, Liu, Jinyang, Wu, Zhiping. 2022. NUDT1 Could Be a Prognostic Biomarker and Correlated with Immune Infiltration in Clear Cell Renal Cell Carcinoma. In Applied bionics and biomechanics, 2022, 3669296. doi:10.1155/2022/3669296. https://pubmed.ncbi.nlm.nih.gov/36606241/
8. Bialkowski, Karol, Szpila, Anna. 2021. Specific 8-oxo-dGTPase activity of MTH1 (NUDT1) protein as a quantitative marker and prognostic factor in human colorectal cancer. In Free radical biology & medicine, 176, 257-264. doi:10.1016/j.freeradbiomed.2021.10.004. https://pubmed.ncbi.nlm.nih.gov/34624481/
9. Tong, Shiao, Xia, Minqi, Xu, Yang, Ye, Zhang, Tian, Daofeng. 2023. Identification and validation of a novel prognostic signature based on mitochondria and oxidative stress related genes for glioblastoma. In Journal of translational medicine, 21, 136. doi:10.1186/s12967-023-03970-6. https://pubmed.ncbi.nlm.nih.gov/36814293/
10. Lau, Hui-Ching, Yuan, Xiaohui, Huang, Huiying, Hsueh, Chi-Yao, Gong, Hongli. 2023. Fusobacterium nucleatum facilitates proliferation and autophagy by activating miR-361-3p/NUDT1 axis through oxidative stress in hypopharyngeal squamous cell carcinoma. In BMC cancer, 23, 990. doi:10.1186/s12885-023-11439-4. https://pubmed.ncbi.nlm.nih.gov/37848855/