Map3k21-flox 基因敲除小鼠

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产品名称

Map3k21-flox 基因敲除小鼠

产品编号

S-CKO-07783

品系全称

C57BL/6JCya-Map3k21em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-234878-Map3k21-B6J-VA

品系状态

使用本品系发表的文献需注明: Map3k21-flox 基因敲除小鼠 mice (Strain S-CKO-07783) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO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 21
基因别称
Mlk4,mKIAA1804
染色体号
Chr 8 (Mouse)
转录本 ID
NCBI: NM_145608 | Ensembl: ENSMUST00000034316
修饰方式
条件性基因敲除
靶向范围
Exon 2~4
敲除长度
~5.9 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
MAP3K21,也称为Mixed lineage kinase 4(MLK4),是一种丝氨酸/苏氨酸激酶,属于混合谱系激酶(MLKs)家族。MLK4在细胞信号传导中发挥着关键作用,通过调节细胞增殖、凋亡、迁移和DNA损伤反应等过程,参与多种生物学功能的调控。MLK4通过磷酸化下游的MEK/ERK(MAPK/ERK)信号通路,影响细胞的增殖、分化和存活。此外,MLK4还与NF-κB信号通路相互作用,参与炎症反应和免疫调节。

MLK4在多种疾病中发挥重要作用,包括结直肠癌、三阴性乳腺癌、系统性红斑狼疮和宫颈癌等。研究表明,MLK4在结直肠癌中频繁突变,与KRAS或BRAF基因突变共同促进肿瘤的发生和发展。MLK4的过表达与三阴性乳腺癌的化疗耐药性相关,抑制MLK4的表达可以增加肿瘤细胞对化疗药物的敏感性。在系统性红斑狼疮中,MLK4的表达异常,与T细胞的活化异常和自身免疫反应有关。MLK4在宫颈癌中的表达水平与肿瘤的侵袭性相关,MLK4的高表达与免疫细胞浸润的减少相关。

MLK4的基因多态性与儿童肥胖的发生相关。研究表明,MLK4基因中的单核苷酸多态性(SNP)与儿童肥胖的易感性相关,并且MLK4的表达水平与肥胖相关的基因的表达水平相关。此外,MLK4的表达与猪大肠杆菌F4ab/ac诱导的腹泻相关。研究表明,MLK4在猪大肠杆菌F4ab/ac感染的大肠上皮细胞中的表达发生改变,与宿主细胞对大肠杆菌感染的免疫反应相关。

综上所述,MLK4是一种重要的丝氨酸/苏氨酸激酶,通过调节细胞信号传导参与多种生物学功能的调控。MLK4在多种疾病中发挥重要作用,包括结直肠癌、三阴性乳腺癌、系统性红斑狼疮和宫颈癌等。此外,MLK4的基因多态性与儿童肥胖的发生相关,MLK4的表达与猪大肠杆菌F4ab/ac诱导的腹泻相关。MLK4的研究有助于深入理解MLK4在疾病发生发展中的作用机制,为疾病的治疗和预防提供新的思路和策略[1][2][3][4][5][6][7][8][9][10]。

参考文献:
1. Aglago, Elom K, Qu, Conghui, Harlid, Sophia, van Guelpen, Bethany, Peters, Ulrike. 2024. Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing. In The American journal of clinical nutrition, 120, 664-673. doi:10.1016/j.ajcnut.2024.07.012. https://pubmed.ncbi.nlm.nih.gov/39025327/
2. Mao, Ke, Zhang, Meixian, Cao, Jinshuai, Zhang, Yong-Biao, Mi, Jie. . Coding Variants are Relevant to the Expression of Obesity-Related Genes for Pediatric Adiposity. In Obesity (Silver Spring, Md.), 29, 194-203. doi:10.1002/oby.23046. https://pubmed.ncbi.nlm.nih.gov/34494379/
3. Shan, Jingxuan, Chouchane, Aziz, Mokrab, Younes, Bedognetti, Davide, Chouchane, Lotfi. 2019. Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications. In Frontiers in oncology, 9, 1328. doi:10.3389/fonc.2019.01328. https://pubmed.ncbi.nlm.nih.gov/31921621/
4. Chuang, Huai-Chia, Tan, Tse-Hua. 2019. MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus. In Cells, 8, . doi:10.3390/cells8111433. https://pubmed.ncbi.nlm.nih.gov/31766293/
5. Mehlich, Dawid, Łomiak, Michał, Sobiborowicz, Aleksandra, Nowis, Dominika, Marusiak, Anna A. 2021. MLK4 regulates DNA damage response and promotes triple-negative breast cancer chemoresistance. In Cell death & disease, 12, 1111. doi:10.1038/s41419-021-04405-0. https://pubmed.ncbi.nlm.nih.gov/34839359/
6. Wang, Wenwen, Zhou, Chuanli, Tang, Hui, Yu, Ying, Zhang, Qin. 2020. Combined Analysis of DNA Methylome and Transcriptome Reveal Novel Candidate Genes Related to Porcine Escherichia coli F4ab/ac-Induced Diarrhea. In Frontiers in cellular and infection microbiology, 10, 250. doi:10.3389/fcimb.2020.00250. https://pubmed.ncbi.nlm.nih.gov/32547963/
7. Gong, Meng, Shen, Fujin, Li, Yang, Ming, Lei, Hong, Li. 2023. MLK4 as an immune marker and its correlation with immune infiltration in Cervical squamous cell carcinoma and endocervical adenocarcinoma(CESC). In PloS one, 18, e0290462. doi:10.1371/journal.pone.0290462. https://pubmed.ncbi.nlm.nih.gov/37594950/
8. Kim, Sung-Hak, Ezhilarasan, Ravesanker, Phillips, Emma, Bhat, Krishna P, Nakano, Ichiro. . Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-dependent Manner. In Cancer cell, 29, 201-13. doi:10.1016/j.ccell.2016.01.005. https://pubmed.ncbi.nlm.nih.gov/26859459/
9. Banos, Georgios, Lindsay, Victoria, Desta, Takele T, Hanotte, Olivier, Psifidi, Androniki. 2020. Integrating Genetic and Genomic Analyses of Combined Health Data Across Ecotypes to Improve Disease Resistance in Indigenous African Chickens. In Frontiers in genetics, 11, 543890. doi:10.3389/fgene.2020.543890. https://pubmed.ncbi.nlm.nih.gov/33193617/
10. Martini, Miriam, Russo, Mariangela, Lamba, Simona, Marchetti, Antonio, Bardelli, Alberto. 2013. Mixed lineage kinase MLK4 is activated in colorectal cancers where it synergistically cooperates with activated RAS signaling in driving tumorigenesis. In Cancer research, 73, 1912-21. doi:10.1158/0008-5472.CAN-12-3074. https://pubmed.ncbi.nlm.nih.gov/23319808/