Pla2g4a-flox 基因敲除小鼠

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产品名称

Pla2g4a-flox 基因敲除小鼠

产品编号

S-CKO-18108

品系全称

C57BL/6JCya-Pla2g4aem1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-18783-Pla2g4a-B6J-VB

品系状态

使用本品系发表的文献需注明: Pla2g4a-flox 基因敲除小鼠 mice (Strain S-CKO-18108) 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
phospholipase A2, group IVA (cytosolic, calcium-dependent)
基因别称
Pla2g4,cPLA2,cPLA2-alpha,cPLA2alpha
染色体号
Chr 1 (Mouse)
转录本 ID
NCBI: NM_008869 | Ensembl: ENSMUST00000070200
修饰方式
条件性基因敲除
靶向范围
Exon 4~5
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:1195256Mice homozygouse for disruptions in this gene display reduced allergic and autoimmune reactions. They also display an increased incidence of insulin and reduced female reproductive performance.
Pla2g4a,也称为磷脂酶A2组IVa(cPLA2),是一种重要的细胞质磷脂酶。cPLA2在细胞中负责催化磷脂的降解,生成花生四烯酸,后者是多种生物活性脂质如前列腺素和白三烯的前体。cPLA2的表达和活性受到多种信号通路的调控,包括MAPK、PI3K/AKT、NF-κB等。cPLA2在多种生物学过程中发挥作用,包括炎症、免疫、细胞增殖和凋亡。

cPLA2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,cPLA2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,cPLA2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,cPLA2通过m6A修饰抑制SOX4 mRNA的表达,从而抑制肿瘤的转移[3]。此外,cPLA2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,cPLA2表达显著上调,与不良预后有强相关性。cPLA2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]。cPLA2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]。

cPLA2不仅在RNA修饰中发挥作用,还具有独立的染色质调控功能。cPLA2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,cPLA2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,cPLA2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。cPLA2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,cPLA2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。cPLA2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. Jin, Weili, Zhao, Jixing, Yang, Eryan, Zhou, Junhu, Kang, Chunsheng. 2022. Neuronal STAT3/HIF-1α/PTRF axis-mediated bioenergetic disturbance exacerbates cerebral ischemia-reperfusion injury via PLA2G4A. In Theranostics, 12, 3196-3216. doi:10.7150/thno.71029. https://pubmed.ncbi.nlm.nih.gov/35547748/
2. Luo, Yuanyuan, Liu, Lerong, Zhang, Cheng. 2023. Identification and analysis of diverse cell death patterns in diabetic kidney disease using microarray-based transcriptome profiling and single-nucleus RNA sequencing. In Computers in biology and medicine, 169, 107780. doi:10.1016/j.compbiomed.2023.107780. https://pubmed.ncbi.nlm.nih.gov/38104515/
3. Plastira, Ioanna, Bernhart, Eva, Joshi, Lisha, Malle, Ernst, Sattler, Wolfgang. 2020. MAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia. In Journal of neuroinflammation, 17, 127. doi:10.1186/s12974-020-01809-1. https://pubmed.ncbi.nlm.nih.gov/32326963/
4. Chen, Menglin, Zhang, Cancan, Li, Huaizhi, Wu, Jian, Sun, Qingmin. 2024. PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer. In Journal of translational medicine, 22, 249. doi:10.1186/s12967-024-05055-4. https://pubmed.ncbi.nlm.nih.gov/38454407/
5. Nadalin, Sergej, Buretić-Tomljanović, Alena. 2018. An association between the BanI polymorphism of the PLA2G4A gene for calcium-dependent phospholipase A2 and plasma glucose levels among females with schizophrenia. In Prostaglandins, leukotrienes, and essential fatty acids, 135, 39-41. doi:10.1016/j.plefa.2018.06.007. https://pubmed.ncbi.nlm.nih.gov/30103930/
6. Nadalin, Sergej, Giacometti, Jasminka, Jonovska, Suzana, Tomljanović, Draško, Buretić-Tomljanović, Alena. 2012. The impact of PLA2G4A and PTGS2 gene polymorphisms, and red blood cell PUFAs deficit on niacin skin flush response in schizophrenia patients. In Prostaglandins, leukotrienes, and essential fatty acids, 88, 185-90. doi:10.1016/j.plefa.2012.11.005. https://pubmed.ncbi.nlm.nih.gov/23219238/
7. Xiong, Jiahui, Lai, Yongping, Cheng, Niangmei, Zhao, Bixing, Yang, Xiaoyu. 2023. Lnc-PLA2G4A-4 facilitates the progression of hepatocellular carcinoma by inducing versican expression via sponging miR-23b-3p. In Heliyon, 9, e18698. doi:10.1016/j.heliyon.2023.e18698. https://pubmed.ncbi.nlm.nih.gov/37554815/
8. Gao, Zibo, Guo, Xinru, Sun, Zhouyang, Bai, Wei, Kou, Changgui. 2024. Copy number deletion of PLA2G4A affects the susceptibility and clinical phenotypes of schizophrenia. In Schizophrenia (Heidelberg, Germany), 10, 55. doi:10.1038/s41537-024-00474-0. https://pubmed.ncbi.nlm.nih.gov/38816399/