Map3k5-KO 基因敲除小鼠

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产品名称

Map3k5-KO 基因敲除小鼠

产品编号

S-KO-08491

品系全称

C57BL/6JCya-Map3k5em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-26408-Map3k5-B6J-VA

品系状态

使用本品系发表的文献需注明: Map3k5-KO 基因敲除小鼠 mice (Strain S-KO-08491) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
KO小鼠库模型
MAPK信号通路

基本信息

基因研究概述

质控标准

基因
基因全称
mitogen-activated protein kinase kinase kinase 5
基因别称
7420452D20Rik,ASK,ASK1,MAPKKK5,Mekk5
染色体号
Chr 10 (Mouse)
转录本 ID
NCBI: NM_008580.4 | Ensembl: ENSMUST00000095806
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:1346876Homozygous mutant mice are overtly normal, however apoptosis abnormalities are evident in cultured cells and after induced heart damage.
MAP3K5,也称为凋亡信号调节激酶1(ASK1),是一种重要的丝裂原活化蛋白激酶激酶激酶(MAP3Ks)。MAP3Ks在细胞信号转导中发挥核心作用,通过MAP激酶(MAPKs)级联反应调节细胞增殖、分化、存活和凋亡等生物学过程。MAP3K5主要参与调节促凋亡信号通路,如细胞应激、炎症和氧化应激等。在细胞应激条件下,MAP3K5被激活并激活下游的MAPKs,如JNK和p38,进而诱导细胞凋亡。MAP3K5还参与调节细胞代谢、免疫反应和肿瘤发生等生物学过程。

MAP3K5在多种疾病中发挥重要作用,包括糖尿病心肌病、非酒精性脂肪性肝炎(NASH)、阿尔茨海默病(AD)、骨关节炎(OA)和肝硬化等。在糖尿病心肌病中,MAP3K5通过JNK/p38信号通路介导细胞凋亡,导致心肌功能障碍[1]。在NASH中,MAP3K5通过抑制ASK1信号通路,保护肝细胞免受损伤,减轻胰岛素抵抗、肝脂肪变性和炎症反应[2]。在AD中,MAP3K5通过激活JNK信号通路,导致神经元细胞凋亡,参与AD的发生和发展[3]。在OA中,MAP3K5通过调节炎症反应和细胞凋亡,导致关节软骨损伤和骨关节炎的发生[4]。在肝硬化中,MAP3K5通过调节炎症反应和细胞增殖,导致肝纤维化和肝硬化的发展[5]。

此外,MAP3K5还与多种遗传疾病相关,如精神分裂症、β-地中海贫血和长寿等。在精神分裂症中,MAP3K5基因的遗传变异与疾病的发生和发展相关[6]。在β-地中海贫血中,MAP3K5基因的遗传变异与疾病严重程度和羟基脲治疗效果相关[7]。在长寿方面,MAP3K5基因的遗传变异与个体寿命相关,尤其在患有心血管代谢疾病的人群中[8]。

MAP3K5还参与调节细胞自噬和细胞周期等生物学过程。在细胞自噬中,MAP3K5通过激活JNK/p38信号通路,抑制自噬的发生,导致细胞损伤和疾病的发生[9]。在细胞周期中,MAP3K5通过激活JNK信号通路,导致细胞周期阻滞,参与肿瘤的发生和发展[10]。

综上所述,MAP3K5是一种重要的信号转导分子,在多种生物学过程中发挥重要作用。MAP3K5在多种疾病中发挥重要作用,包括糖尿病心肌病、NASH、AD、OA和肝硬化等。此外,MAP3K5还与多种遗传疾病相关,如精神分裂症、β-地中海贫血和长寿等。MAP3K5的研究有助于深入理解细胞信号转导的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Hu, Yunxiang, Han, Jun, Ding, Shengqiang, Liu, Sanmao, Wang, Hong. 2022. Identification of ferroptosis-associated biomarkers for the potential diagnosis and treatment of postmenopausal osteoporosis. In Frontiers in endocrinology, 13, 986384. doi:10.3389/fendo.2022.986384. https://pubmed.ncbi.nlm.nih.gov/36105394/
2. Luan, Zhilin, Sun, Yang, Li, Yuyuan, Ming, Wenhua, Zhang, Ye. . Genetic association of the human MAP3K5 gene with schizophrenia in a Chinese Han population. In Psychiatric genetics, 29, 26-27. doi:10.1097/YPG.0000000000000213. https://pubmed.ncbi.nlm.nih.gov/30576298/
3. Qian, Weina, Li, Weili, Chen, Xiaoyang, Wang, Yong, Wang, Wei. 2023. Exploring the mechanism of Xingpi Capsule in diarrhea predominant-irritable bowel syndrome treatment based on multiomics technology. In Phytomedicine : international journal of phytotherapy and phytopharmacology, 111, 154653. doi:10.1016/j.phymed.2023.154653. https://pubmed.ncbi.nlm.nih.gov/36641976/
4. Zhou, Jing, Li, Xin-Yu, Liu, Yu-Jia, Shen, Han-Ming, Lu, Guo-Dong. 2021. Full-coverage regulations of autophagy by ROS: from induction to maturation. In Autophagy, 18, 1240-1255. doi:10.1080/15548627.2021.1984656. https://pubmed.ncbi.nlm.nih.gov/34662529/
5. Lan, Tian, Hu, Yufeng, Hu, Fengjiao, Rong, Xianglu, Guo, Jiao. 2021. Hepatocyte glutathione S-transferase mu 2 prevents non-alcoholic steatohepatitis by suppressing ASK1 signaling. In Journal of hepatology, 76, 407-419. doi:10.1016/j.jhep.2021.09.040. https://pubmed.ncbi.nlm.nih.gov/34656650/
6. Wang, Kehan, Kong, Feifei, Qiu, Yuexin, Hu, Zhibin, Li, Jing. 2023. Autophagy regulation and protein kinase activity of PIK3C3 controls sertoli cell polarity through its negative regulation on SCIN (scinderin). In Autophagy, 19, 2934-2957. doi:10.1080/15548627.2023.2235195. https://pubmed.ncbi.nlm.nih.gov/37450577/
7. Tafrali, Christina, Paizi, Arsinoi, Borg, Joseph, Georgitsi, Marianthi, Patrinos, George P. . Genomic variation in the MAP3K5 gene is associated with β-thalassemia disease severity and hydroxyurea treatment efficacy. In Pharmacogenomics, 14, 469-83. doi:10.2217/pgs.13.31. https://pubmed.ncbi.nlm.nih.gov/23556445/
8. Morris, Brian J, Chen, Randi, Donlon, Timothy A, Allsopp, Richard C, Willcox, Bradley J. 2021. Lifespan extension conferred by mitogen-activated protein kinase kinase kinase 5 (MAP3K5) longevity-associated gene variation is confined to at-risk men with a cardiometabolic disease. In Aging, 13, 7953-7974. doi:10.18632/aging.202844. https://pubmed.ncbi.nlm.nih.gov/33739303/
9. Zeng, Zhi, Xia, Luoxing, Fan, Shunyang, Liu, Renjing, Tang, Wai Ho. 2020. Circular RNA CircMAP3K5 Acts as a MicroRNA-22-3p Sponge to Promote Resolution of Intimal Hyperplasia Via TET2-Mediated Smooth Muscle Cell Differentiation. In Circulation, 143, 354-371. doi:10.1161/CIRCULATIONAHA.120.049715. https://pubmed.ncbi.nlm.nih.gov/33207953/
10. Zhou, Liang, Li, Youyou, Li, Jiaren, Li, Cheng, Wang, Long. 2023. Multi-omics analysis to identify CBR3-AS1-hsa-miR-145-5p-MAP3K5 pathway as a ferroptosis-related ceRNA network in benign prostatic hyperplasia. In Genes & diseases, 11, 101184. doi:10.1016/j.gendis.2023.101184. https://pubmed.ncbi.nlm.nih.gov/38882013/