Trmt5-KO 基因敲除小鼠

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产品名称

Trmt5-KO 基因敲除小鼠

产品编号

S-KO-14838

品系全称

C57BL/6JCya-Trmt5em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-76357-Trmt5-B6J-VA

品系状态

使用本品系发表的文献需注明: Trmt5-KO 基因敲除小鼠 mice (Strain S-KO-14838) 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
TRM5 tRNA methyltransferase 5
基因别称
2610027O18Rik,mKIAA1393
染色体号
Chr 12 (Mouse)
转录本 ID
NCBI: NM_029580 | Ensembl: ENSMUST00000116420
修饰方式
全身性基因敲除
靶向范围
Exon 3
敲除长度
~0.1 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:1923607Mice homozygous for a knock-out allele show complete embryonic lethality between implantation and somite formation.
Trmt5(tRNA甲基转移酶5)是一种线粒体蛋白质,属于I类甲基转移酶超家族。它在tRNA的转录后修饰过程中发挥着关键作用,催化线粒体tRNA中第37位鸟苷的m1G37甲基化修饰。tRNA的这种修饰对于维持线粒体功能和能量代谢至关重要。

越来越多的研究表明,Trmt5在多种疾病中发挥着重要作用。在肝癌中,Trmt5的表达上调与不良预后相关。敲低Trmt5可以抑制肝癌细胞的增殖和转移,并提高癌细胞对化疗药物的敏感性[1]。在缺血性心肌病中,Trmt5的表达显著上调,其缺失可以增强线粒体膜电位并减少细胞凋亡,从而改善心肌细胞的功能[2]。此外,Trmt5的突变也与多种线粒体疾病相关,包括线粒体呼吸链缺陷、肝肺综合征和脱髓鞘性周围神经病[4,5,6]。

Trmt5的缺失还与自发性炎症性肠病样表型相关。在斑马鱼模型中,Trmt5的缺失导致肠炎样表型,提示Trmt5在维持肠道免疫稳态和预防炎症性疾病中发挥作用[3]。此外,Trmt5的突变还与遗传性神经病综合征相关,表现为生长迟缓、运动发育迟缓、智力障碍和严重的脱髓鞘性周围神经病[4]。

Trmt5的缺失还导致线粒体tRNA的m1G37修饰缺陷,进而导致线粒体呼吸链复合物活性降低,引起能量代谢障碍[7]。这种缺陷在骨骼肌中尤为明显,可能与Trmt5在骨骼肌中的高表达有关。此外,肥胖诱导的循环免疫细胞可以通过释放含有miR-3960的小RNA,靶向Trmt5基因,导致线粒体tRNA的m1G37修饰缺陷,进而引起肾小管细胞线粒体功能障碍,加剧肾脏损伤[8]。

综上所述,Trmt5在维持线粒体功能和能量代谢中发挥着重要作用。Trmt5的缺失或突变与多种疾病相关,包括肝癌、缺血性心肌病、线粒体疾病、炎症性肠病和遗传性神经病综合征。研究Trmt5的功能和调控机制,有助于深入理解线粒体疾病的发病机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Zhao, Qiong, Zhang, Luwen, He, Qiufen, Pan, Ruolang, Chen, Ye. . Targeting TRMT5 suppresses hepatocellular carcinoma progression via inhibiting the HIF-1α pathways. In Journal of Zhejiang University. Science. B, 24, 50-63. doi:10.1631/jzus.B2200224. https://pubmed.ncbi.nlm.nih.gov/36632750/
2. Song, Huafeng, Chen, Shaoze, Zhang, Tingting, Wu, Yueheng, Liu, Youbin. 2022. Integrated Strategies of Diverse Feature Selection Methods Identify Aging-Based Reliable Gene Signatures for Ischemic Cardiomyopathy. In Frontiers in molecular biosciences, 9, 805235. doi:10.3389/fmolb.2022.805235. https://pubmed.ncbi.nlm.nih.gov/35300115/
3. Zhao, Qiong, Chang, Hui, Zheng, Jing, Zhao, Robert Chunhua, Chen, Ye. 2023. A novel Trmt5-deficient zebrafish model with spontaneous inflammatory bowel disease-like phenotype. In Signal transduction and targeted therapy, 8, 86. doi:10.1038/s41392-023-01318-6. https://pubmed.ncbi.nlm.nih.gov/36849517/
4. Argente-Escrig, Herminia, Vílchez, Juan J, Frasquet, Marina, Lupo, Vincenzo, Sevilla, Teresa. 2022. A novel TRMT5 mutation causes a complex inherited neuropathy syndrome: The role of nerve pathology in defining a demyelinating neuropathy. In Neuropathology and applied neurobiology, 48, e12817. doi:10.1111/nan.12817. https://pubmed.ncbi.nlm.nih.gov/35342985/
5. Warasnhe, Khaled, Özçay, Figen, Aydin, Halil İbrahim, Özgün, Gonca, Ceylaner, Serdar. 2022. A novel mutation in TRMT5 associated with idiopathic non-cirrhotic portal hypertension and hepatopulmonary syndrome: Case report of two siblings. In Clinics and research in hepatology and gastroenterology, 46, 101928. doi:10.1016/j.clinre.2022.101928. https://pubmed.ncbi.nlm.nih.gov/35460901/
6. Wu, Shuiyan, Li, Weixi, Bai, Zhenjiang, Liu, Ying, Lv, Haitao. 2022. Novel heterozygous compound TRMT5 mutations associated with combined oxidative phosphorylation deficiency 26 in a Chinese family: a case report. In BMC pediatrics, 22, 74. doi:10.1186/s12887-022-03138-z. https://pubmed.ncbi.nlm.nih.gov/35109800/
7. Powell, Christopher A, Kopajtich, Robert, D'Souza, Aaron R, Prokisch, Holger, Minczuk, Michal. 2015. TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies. In American journal of human genetics, 97, 319-28. doi:10.1016/j.ajhg.2015.06.011. https://pubmed.ncbi.nlm.nih.gov/26189817/
8. Li, Xiaqing, Yang, Wah, Ma, Ke, Yin, Lianghong, Meng, Yu. 2024. Circulating B Cell-Derived Small RNA Delivered by Extracellular Vesicles: A Dialogue Mechanism for Long-Range Targeted Renal Mitochondrial Injury in Obesity. In Small (Weinheim an der Bergstrasse, Germany), 20, e2402526. doi:10.1002/smll.202402526. https://pubmed.ncbi.nlm.nih.gov/38958071/