Rras-KO 基因敲除小鼠

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产品名称

Rras-KO 基因敲除小鼠

产品编号

S-KO-04161

品系全称

C57BL/6JCya-Rrasem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-20130-Rras-B6J-VA

品系状态

使用本品系发表的文献需注明: Rras-KO 基因敲除小鼠 mice (Strain S-KO-04161) 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
related RAS viral (r-ras) oncogene
基因别称
Rras1
染色体号
Chr 7 (Mouse)
转录本 ID
NCBI: NM_009101 | Ensembl: ENSMUST00000044111
修饰方式
全身性基因敲除
靶向范围
Exon 2~6
敲除长度
~1.8 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:98179Homozygote and heterozygote null mice are lymphopenic, resulting from diminished homeostatic proliferation and impaired T cell and B cell survival. Mice homozygous for a gene-trapped allele exhibit enhanced neointimal thickening in response to arterial injury, increased angiogenesis in matrigel plugs and aortic ring cultures, and increased neovascularization of tumor implants, and decreased B-cell and increased T-cell population percentages.
Rras,全称为Ras-related protein,是一种小分子量的GTP酶,属于Ras家族。Rras在细胞信号传导中起着重要作用,主要参与调控细胞生长、分化和存活。Rras在多种生物学过程中发挥着关键作用,包括细胞信号传导、细胞周期调控、细胞凋亡和肿瘤发生等。

Rras在多种疾病中发挥重要作用,包括动脉粥样硬化、糖尿病心肌病、结直肠癌和Wilms瘤。在动脉粥样硬化中,Rras通过NF-κB/IL-6信号通路介导巨噬细胞的炎症反应,促进动脉粥样硬化斑块的形成[1]。在糖尿病心肌病中,Rras通过下调lncRNA TINCR抑制焦亡和糖尿病心肌病的发生[2]。在结直肠癌中,Rras通过m6A修饰抑制SOX4 mRNA的表达,从而抑制肿瘤的转移[3]。此外,Rras的基因多态性与中国儿童Wilms瘤的易感性降低相关[4]。

高风险神经母细胞瘤(NB)患者中,Rras表达显著上调,与不良预后有强相关性。Rras通过m6A-YTHDF1依赖机制抑制YWHAH表达,激活PI3K/AKT信号通路,促进NB细胞活性[5]。Rras通过促进PRC2和KDM5B在二价结构域上的结合,影响组蛋白修饰,进而调控二价结构基因的表达[6]

Rras不仅在RNA修饰中发挥作用,还具有独立的染色质调控功能。Rras可以与H3K27me3结合,招募KDM6B诱导H3K27me3的去甲基化,从而影响基因表达和干细胞的多能性维持[7]。此外,Rras还可以通过下调lncRNA XIST的表达抑制结直肠癌的增殖和转移[8]。

综上所述,Rras是一种重要的RNA甲基转移酶,参与调控RNA的稳定性和功能,影响基因表达和生物学过程。Rras在多种疾病中发挥重要作用,包括动脉粥样硬化、糖尿病心肌病、结直肠癌和Wilms瘤。此外,Rras还具有独立的染色质调控功能,影响基因表达和干细胞的多能性维持。Rras的研究有助于深入理解RNA表观遗传修饰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. Bian, Fenghua, Lan, Ying-Wei, Zhao, Shuyang, Kalinichenko, Vladimir V, Kalin, Tanya V. 2023. Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling. In Nature communications, 14, 2560. doi:10.1038/s41467-023-38177-2. https://pubmed.ncbi.nlm.nih.gov/37137915/
2. Xiao, Ruowen, Shi, Lu, Yang, Te, Wang, Huiyun, Mai, Shijuan. . Identification of RRAS gene related to nasopharyngeal carcinoma based on pathway and network-based analyses. In Translational cancer research, 8, 664-675. doi:10.21037/tcr.2019.04.04. https://pubmed.ncbi.nlm.nih.gov/35116799/
3. Mora, Johanna, Palmer, Rachel, Wagner, Leslie, Song, Sam, Thacker, Seth. 2024. 2023 White Paper on Recent Issues in Bioanalysis: ISR for ADA Assays, the Rise of dPCR vs qPCR, International Reference Standards for Vaccine Assays, Anti-AAV TAb Post-Dose Assessment, NanoString Validation, ELISpot as Gold Standard (Part 3 - Recommendations on Gene Therapy, Cell Therapy, Vaccines Immunogenicity & Technologies; Biotherapeutics Immunogenicity & Risk Assessment; ADA/NAb Assay/Reporting Harmonization). In Bioanalysis, 16, 77-119. doi:10.4155/bio-2024-0024. https://pubmed.ncbi.nlm.nih.gov/38389403/
4. Flex, Elisabetta, Jaiswal, Mamta, Pantaleoni, Francesca, Ahmadian, Mohammad R, Tartaglia, Marco. 2014. Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis. In Human molecular genetics, 23, 4315-27. doi:10.1093/hmg/ddu148. https://pubmed.ncbi.nlm.nih.gov/24705357/
5. Bos, J L. . Ras-like GTPases. In Biochimica et biophysica acta, 1333, M19-31. doi:. https://pubmed.ncbi.nlm.nih.gov/9395281/
6. Aoki, Yoko, Niihori, Tetsuya, Inoue, Shin-ichi, Matsubara, Yoichi. 2015. Recent advances in RASopathies. In Journal of human genetics, 61, 33-9. doi:10.1038/jhg.2015.114. https://pubmed.ncbi.nlm.nih.gov/26446362/
7. Xu, Ming-yan, Fu, Yu-cai, Liu, Ju-li, Zhang, Ren-li. . [Molecular cloning and characterization of a RRas homologue gene from Trichomonas vaginalis]. In Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases, 24, 215-8. doi:. https://pubmed.ncbi.nlm.nih.gov/17094627/
8. Zhao, Rui, Li, Hao, Shen, Chun, Zheng, Shan. . RRAS: A key regulator and an important prognostic biomarker in biliary atresia. In World journal of gastroenterology, 17, 796-803. doi:10.3748/wjg.v17.i6.796. https://pubmed.ncbi.nlm.nih.gov/21390152/