Rragc-KO 基因敲除小鼠

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产品名称

Rragc-KO 基因敲除小鼠

产品编号

S-KO-10481

品系全称

C57BL/6JCya-Rragcem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-54170-Rragc-B6J-VA

品系状态

使用本品系发表的文献需注明: Rragc-KO 基因敲除小鼠 mice (Strain S-KO-10481) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
KO小鼠库模型
mTOR信号通路

基本信息

基因研究概述

质控标准

基因
基因全称
Ras-related GTP binding C
基因别称
Gtr2,RAGC,TIB929,YGR163W
染色体号
Chr 4 (Mouse)
转录本 ID
NCBI: NM_017475 | Ensembl: ENSMUST00000030399
修饰方式
全身性基因敲除
靶向范围
Exon 3~5
敲除长度
~4.8 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:1858751Mice homozygous for a hypomorphic allele show complete preweaning lethality, with partial embryonic observed at E13.5. Heterozygotes exhibit attenuated nutrient signaling and impaired B cell activation upon immunization but show normal longevity and normal age-dependent health decline.
RRAGC,也称为Ras-related GTP binding C,是一种Ras相关GTP结合蛋白,是mTORC1信号通路的重要组成部分。mTORC1是细胞生长、代谢和增殖的关键调节因子,对营养状态、生长因子和能量水平等信号做出反应。RRAGC与另一个Ras相关GTP结合蛋白RRAGA形成异源二聚体,与RPTOR(raptor)相互作用,将细胞内的氨基酸浓度信号传递给mTORC1,从而调节mTORC1的活性。

RRAGC在多种生物学过程中发挥重要作用,包括细胞生长、代谢和增殖。在非酒精性脂肪肝病(NAFLD)中,STING1的激活可以促进RRAGC与mTORC1复合物的形成,进而激活mTORC1,抑制脂质降解,导致肝细胞内脂质积累[1]。在淋巴瘤中,RRAGC的突变可以导致mTORC1的过度激活,促进肿瘤细胞的生长和增殖[2][3][4]。在口腔鳞状细胞癌中,RRAGC的表达水平与肿瘤的进展和预后相关[10]。

RRAGC的表达和活性受到多种因素的调节,包括表观遗传修饰、转录因子和信号通路。例如,EHMT2可以抑制RRAGC的表达,而ROS可以激活RRAGC的表达[7]。此外,TFEB和TFE3可以与FACT复合物相互作用,调节RRAGC的表达[6]。

RRAGC的研究对于深入理解mTORC1信号通路的调控机制和其在疾病发生发展中的作用具有重要意义。RRAGC的突变和表达异常与多种疾病的发生发展相关,包括非酒精性脂肪肝病、淋巴瘤和口腔鳞状细胞癌等。因此,RRAGC可以作为潜在的药物靶点,为相关疾病的治疗提供新的思路和策略。

参考文献:
1. Liu, Kunpeng, Qiu, Dongbo, Liang, Xue, Qin, Yunfei, Zhang, Qi. 2021. Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy. In Autophagy, 18, 860-876. doi:10.1080/15548627.2021.1961072. https://pubmed.ncbi.nlm.nih.gov/34382907/
2. Reijnders, Margot R F, Seibt, Annette, Brugger, Melanie, Poulter, James A, Distelmaier, Felix. 2023. De novo missense variants in RRAGC lead to a fatal mTORopathy of early childhood. In Genetics in medicine : official journal of the American College of Medical Genetics, 25, 100838. doi:10.1016/j.gim.2023.100838. https://pubmed.ncbi.nlm.nih.gov/37057673/
3. Okosun, Jessica, Wolfson, Rachel L, Wang, Jun, Sabatini, David M, Fitzgibbon, Jude. 2015. Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma. In Nature genetics, 48, 183-8. doi:10.1038/ng.3473. https://pubmed.ncbi.nlm.nih.gov/26691987/
4. Ying, Zhang Xiao, Jin, Meiyan, Peterson, Luke F, Klionsky, Daniel J, Malek, Sami N. 2016. Recurrent Mutations in the MTOR Regulator RRAGC in Follicular Lymphoma. In Clinical cancer research : an official journal of the American Association for Cancer Research, 22, 5383-5393. doi:. https://pubmed.ncbi.nlm.nih.gov/27267853/
5. Meng, Yu, Zhou, Mengyu, Wang, Tuanwei, Liu, Yun, Xia, Zhao-Lin. 2022. Occupational lead exposure on genome-wide DNA methylation and DNA damage. In Environmental pollution (Barking, Essex : 1987), 304, 119252. doi:10.1016/j.envpol.2022.119252. https://pubmed.ncbi.nlm.nih.gov/35385786/
6. Jeong, Eutteum, Martina, José A, Contreras, Pablo S, Lee, Juhyung, Puertollano, Rosa. 2022. The FACT complex facilitates expression of lysosomal and antioxidant genes through binding to TFEB and TFE3. In Autophagy, 18, 2333-2349. doi:10.1080/15548627.2022.2029671. https://pubmed.ncbi.nlm.nih.gov/35230915/
7. Hwang, Supyong, Kim, Soyoung, Kim, Kyungkon, Park, Sojung, Kim, Inki. . Euchromatin histone methyltransferase II (EHMT2) regulates the expression of ras-related GTP binding C (RRAGC) protein. In BMB reports, 53, 576-581. doi:. https://pubmed.ncbi.nlm.nih.gov/32684241/
8. Long, Pamela A, Zimmermann, Michael T, Kim, Maengjo, Xu, Xiaolei, Olson, Timothy M. 2016. De novo RRAGC mutation activates mTORC1 signaling in syndromic fetal dilated cardiomyopathy. In Human genetics, 135, 909-917. doi:10.1007/s00439-016-1685-3. https://pubmed.ncbi.nlm.nih.gov/27234373/
9. Yen, Tzu-Li, Huang, Tzyy-Nan, Lin, Ming-Hui, Lerch, Jason, Hsueh, Yi-Ping. . Sex bias in social deficits, neural circuits and nutrient demand in Cttnbp2 autism models. In Brain : a journal of neurology, 146, 2612-2626. doi:10.1093/brain/awac429. https://pubmed.ncbi.nlm.nih.gov/36385662/
10. Suhr, Mai Lill, Dysvik, Bjarte, Bruland, Ove, Vasstrand, Endre N, Ibrahim, Salah O. . Gene expression profile of oral squamous cell carcinomas from Sri Lankan betel quid users. In Oncology reports, 18, 1061-75. doi:. https://pubmed.ncbi.nlm.nih.gov/17914555/