Lrrc8a-flox 基因敲除小鼠

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产品名称

Lrrc8a-flox 基因敲除小鼠

产品编号

S-CKO-17808

品系全称

C57BL/6NCya-Lrrc8aem1flox/Cya

品系背景

C57BL/6NCya

品系编号

CKOCMP-241296-Lrrc8a-B6N-VA

品系状态

使用本品系发表的文献需注明: Lrrc8a-flox 基因敲除小鼠 mice (Strain S-CKO-17808) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
leucine rich repeat containing 8A VRAC subunit A
基因别称
Lrrc8,SWELL1,ebo,mKIAA1437
染色体号
Chr 2 (Mouse)
转录本 ID
NCBI: NM_177725 | Ensembl: ENSMUST00000095078
修饰方式
条件性基因敲除
靶向范围
Exon 3
敲除长度
~2.9 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
MGI:2652847Homozygous for a knock-out allele exhibit prenatal lethality and premature death, growth retardation, sterility, multiple tissue abnormalities, a severe block in early thymic development, and impaired peripheral T cell function. B cell development is modestly impaired but B cell function is normal.

发表文献

Theranostics
2022-07-02
LRRC8A critically regulates myofibroblast phenotypes and fibrotic remodeling following myocardial infarction
1
Lrrc8a,也称为SWELL1,是体积调节的阴离子通道(VRAC)的组成部分。VRAC是一种细胞膜蛋白,负责调节细胞体积和离子平衡。LRRC8A在多种细胞类型中表达,并在细胞对渗透压变化的响应中发挥着关键作用。LRRC8A通道在细胞肿胀时被激活,并允许阴离子和水的流入,从而恢复细胞体积和离子平衡。

LRRC8A在多种疾病中发挥着重要作用,包括脑缺血、胃癌、食管癌、骨肉瘤和头颈癌。在脑缺血中,LRRC8A在星形胶质细胞中表达,并通过释放谷氨酸来调节突触传递和神经元兴奋性。LRRC8A的缺失可以减少谷氨酸的释放,从而保护神经元免受缺血性脑损伤[1]。在胃癌中,LRRC8A的表达与肿瘤的生长和转移有关。LRRC8A的敲低可以抑制胃癌细胞的增殖和迁移,并增强细胞凋亡[2]。LRRC8A的表达水平还与食管癌的病理N和T阶段相关,高表达LRRC8A与食管癌的不良预后相关[4]。LRRC8A在骨肉瘤组织中高表达,并且其表达水平与肿瘤的恶性程度相关[5]。在头颈癌中,LRRC8A的表达水平与铂类药物治疗的反应有关。LRRC8A的缺失可以降低铂类药物的疗效,导致患者生存率下降[6]。

LRRC8A的缺失还会影响T淋巴细胞的发育和功能。LRRC8A在胸腺细胞中的表达水平高于其他免疫细胞,并且LRRC8A的缺失会导致胸腺发育受阻和T细胞功能受损[3]。

LRRC8A还参与调节细胞对高渗透压应激的响应。在高渗透压条件下,LRRC8A通道被激活,允许氯离子的外流,从而促进电解质内流和细胞体积的恢复[7]。

LRRC8A还与化疗药物耐药性有关。LRRC8A的缺失可以降低铂类药物的疗效,导致患者生存率下降[6]。LRRC8A的表达水平还与结肠癌细胞对奥沙利铂的耐药性有关,LRRC8A的敲低可以抑制结肠癌细胞的耐药性[8]。

LRRC8A通过激活线粒体依赖性凋亡途径来增强胶质瘤细胞对替莫唑胺的敏感性。LRRC8A的下调可以抑制替莫唑胺诱导的胶质瘤细胞生长抑制和凋亡,而LRRC8A的上调可以增强替莫唑胺对胶质瘤细胞的生长抑制和凋亡作用[9]。

综上所述,LRRC8A是一种重要的细胞膜蛋白,参与调节细胞体积和离子平衡。LRRC8A在多种疾病中发挥着重要作用,包括脑缺血、胃癌、食管癌、骨肉瘤和头颈癌。LRRC8A还与T淋巴细胞的发育和功能以及化疗药物耐药性有关。LRRC8A的研究有助于深入理解细胞体积和离子平衡的调节机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Yang, Junhua, Vitery, Maria Del Carmen, Chen, Jianan, Chu, Jiachen, Qiu, Zhaozhu. 2019. Glutamate-Releasing SWELL1 Channel in Astrocytes Modulates Synaptic Transmission and Promotes Brain Damage in Stroke. In Neuron, 102, 813-827.e6. doi:10.1016/j.neuron.2019.03.029. https://pubmed.ncbi.nlm.nih.gov/30982627/
2. Kurashima, Kento, Shiozaki, Atsushi, Kudou, Michihiro, Konishi, Eiichi, Otsuji, Eigo. 2021. LRRC8A influences the growth of gastric cancer cells via the p53 signaling pathway. In Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 24, 1063-1075. doi:10.1007/s10120-021-01187-4. https://pubmed.ncbi.nlm.nih.gov/33864161/
3. Kumar, Lalit, Chou, Janet, Yee, Christina S K, Poliani, P Luigi, Geha, Raif S. 2014. Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function. In The Journal of experimental medicine, 211, 929-42. doi:10.1084/jem.20131379. https://pubmed.ncbi.nlm.nih.gov/24752297/
4. Konishi, Tomoki, Shiozaki, Atsushi, Kosuga, Toshiyuki, Marunaka, Yoshinori, Otsuji, Eigo. 2019. LRRC8A Expression Influences Growth of Esophageal Squamous Cell Carcinoma. In The American journal of pathology, 189, 1973-1985. doi:10.1016/j.ajpath.2019.06.006. https://pubmed.ncbi.nlm.nih.gov/31323188/
5. Zhang, Ningfeng, Deng, Zhiqin, Li, Wencui, Duan, Li, Wang, Daping. 2020. Expression of LRRC8A is elevated in the cytoplasm of osteosarcoma tissues: An immunohistochemical study with tissue microarrays. In Experimental and therapeutic medicine, 21, 71. doi:10.3892/etm.2020.9503. https://pubmed.ncbi.nlm.nih.gov/33365071/
6. Widmer, Carmen A, Klebic, Ismar, Domanitskaya, Natalya, Vens, Conchita, Rottenberg, Sven. . Loss of the volume-regulated anion channel components LRRC8A and LRRC8D limits platinum drug efficacy. In Cancer research communications, 2, 1266-1281. doi:10.1158/2767-9764.CRC-22-0208. https://pubmed.ncbi.nlm.nih.gov/36467895/
7. Serra, Selma A, Stojakovic, Predrag, Amat, Ramon, Valverde, Miguel A, Posas, Francesc. . LRRC8A-containing chloride channel is crucial for cell volume recovery and survival under hypertonic conditions. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2025013118. https://pubmed.ncbi.nlm.nih.gov/34083438/
8. Zhang, Haifeng, Jing, Zhenghui, Liu, Rong, Li, Liangming, Peng, Shuang. 2023. LRRC8A promotes the initial development of oxaliplatin resistance in colon cancer cells. In Heliyon, 9, e16872. doi:10.1016/j.heliyon.2023.e16872. https://pubmed.ncbi.nlm.nih.gov/37313175/
9. Yang, Chao, He, Longshuang, Chen, Gaofei, Ning, Zeqian, Xia, Zhibai. 2018. LRRC8A potentiates temozolomide sensitivity in glioma cells via activating mitochondria-dependent apoptotic pathway. In Human cell, 32, 41-50. doi:10.1007/s13577-018-0221-2. https://pubmed.ncbi.nlm.nih.gov/30426452/

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