Arhgef11-KO 基因敲除小鼠

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产品名称

Arhgef11-KO 基因敲除小鼠

产品编号

S-KO-04933

品系全称

C57BL/6JCya-Arhgef11em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-213498-Arhgef11-B6J-VA

品系状态

使用本品系发表的文献需注明: Arhgef11-KO 基因敲除小鼠 mice (Strain S-KO-04933) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量

基本信息

基因研究概述

质控标准

基因
基因全称
Rho guanine nucleotide exchange factor 11
基因别称
PDZ-RhoGEF,Prg,RhoGEF,mKIAA0380
染色体号
Chr 3 (Mouse)
转录本 ID
NCBI: NM_001003912 | Ensembl: ENSMUST00000039476
修饰方式
全身性基因敲除
靶向范围
Exon 2~7
敲除长度
~5.4 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:2441869Mice homozygous for a knock-out allele exhibit no obvious phenotype.
ARHGEF11,也称为Rho guanine nucleotide exchange factor 11,是一种编码Rho GTPase交换因子11的基因。Rho GTPases是一类重要的信号转导分子,参与调节细胞骨架的重组、细胞迁移、细胞增殖和细胞凋亡等多种生物学过程。ARHGEF11作为Rho GTPases的调节因子,通过激活Rho信号通路,影响细胞的生物学行为。

ARHGEF11在多种疾病中发挥重要作用,包括糖尿病、癌症和肾脏疾病。在糖尿病中,ARHGEF11基因的变异与胰岛素抵抗和2型糖尿病的易感性增加相关[1][6][8]。研究发现,ARHGEF11基因的R1467H变异与Pima印第安人中的胰岛素抵抗和年轻型2型糖尿病相关[1]。在汉族人群中,ARHGEF11基因的R1467H多态性与2型糖尿病和胰岛素抵抗的风险增加相关[8]。此外,ARHGEF11基因的变异还与日本人群中的精神分裂症易感性相关[5]。

在癌症中,ARHGEF11基因的表达和功能异常与肿瘤的发生和发展密切相关。研究发现,ARHGEF11基因的表达在肝细胞癌(HCC)样本和高度转移性肝瘤细胞系中上调,通过激活β-catenin信号通路促进肿瘤的增殖和上皮-间质转化(EMT)[2]。此外,ARHGEF11基因的融合基因与儿童脊髓弥漫性高级别胶质瘤的发生相关,且对Entrectinib治疗有反应[3]。

在肾脏疾病中,ARHGEF11基因的变异与肾脏损伤相关。研究发现,ARHGEF11基因的变异在Dahl盐敏感性大鼠中影响肾脏损伤,通过Rho-ROCK信号通路导致细胞形态改变和肾小管细胞功能受损[7][9]。此外,ARHGEF11基因的表达在正常葡萄糖耐量孕妇中与胎儿巨大型相关,可能通过抑制胎盘胰岛素信号通路参与胎儿过度生长[4]。

综上所述,ARHGEF11基因在多种疾病中发挥重要作用,包括糖尿病、癌症和肾脏疾病。ARHGEF11基因的变异与胰岛素抵抗、2型糖尿病、精神分裂症、肝细胞癌、儿童脊髓弥漫性高级别胶质瘤和肾脏损伤等相关。ARHGEF11基因的功能研究有助于深入理解疾病的发生机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Ma, Lijun, Hanson, Robert L, Que, Lorem N, Shuldiner, Alan R, Baier, Leslie J. 2007. Variants in ARHGEF11, a candidate gene for the linkage to type 2 diabetes on chromosome 1q, are nominally associated with insulin resistance and type 2 diabetes in Pima Indians. In Diabetes, 56, 1454-9. doi:. https://pubmed.ncbi.nlm.nih.gov/17287471/
2. Du, Jinpeng, Zhu, Zexin, Xu, Lin, Yuan, Kefei, Zeng, Yong. 2020. ARHGEF11 promotes proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma through activation of β-catenin pathway. In Aging, 12, 20235-20253. doi:10.18632/aging.103772. https://pubmed.ncbi.nlm.nih.gov/33122451/
3. Miyachi, Mitsuru, Sugimoto, Yohei, Sugitatsu, Yuya, Konishi, Eiichi, Iehara, Tomoko. 2023. Entrectinib treatment induces a durable response against ARHGEF11::NTRK1 fusion gene-positive spinal cord diffuse pediatric-type high-grade glioma. In Pediatric blood & cancer, 70, e30513. doi:10.1002/pbc.30513. https://pubmed.ncbi.nlm.nih.gov/37393426/
4. Zhang, Wanyi, Su, Rina, Lin, Li, Yang, Huixia. 2017. ARHGEF11 affecting the placental insulin signaling pathway in fetal macrosomia of normal glucose tolerance pregnant women. In Placenta, 63, 7-14. doi:10.1016/j.placenta.2017.12.010. https://pubmed.ncbi.nlm.nih.gov/29486856/
5. Mizuki, Yutaka, Takaki, Manabu, Okahisa, Yuko, Ujike, Hiroshi, Uchitomi, Yosuke. 2014. Human Rho guanine nucleotide exchange factor 11 gene is associated with schizophrenia in a Japanese population. In Human psychopharmacology, 29, 552-8. doi:10.1002/hup.2435. https://pubmed.ncbi.nlm.nih.gov/25319871/
6. Fu, Mao, Sabra, Mona M, Damcott, Coleen, Baier, Leslie J, Shuldiner, Alan R. 2007. Evidence that Rho guanine nucleotide exchange factor 11 (ARHGEF11) on 1q21 is a type 2 diabetes susceptibility gene in the Old Order Amish. In Diabetes, 56, 1363-8. doi:. https://pubmed.ncbi.nlm.nih.gov/17369523/
7. Jia, Zhen, Johnson, Ashley C, Wang, Xuexiang, Kyle, Patrick B, Garrett, Michael R. 2015. Allelic Variants in Arhgef11 via the Rho-Rock Pathway Are Linked to Epithelial-Mesenchymal Transition and Contributes to Kidney Injury in the Dahl Salt-Sensitive Rat. In PloS one, 10, e0132553. doi:10.1371/journal.pone.0132553. https://pubmed.ncbi.nlm.nih.gov/26172442/
8. Liu, Jing, Chen, Xiaohui, Guo, Qian, Zhang, Xiaohui, Zhang, Shulan. 2011. Association of ARHGEF11 R1467H polymorphism with risk for type 2 diabetes mellitus and insulin resistance in Chinese population. In Molecular biology reports, 38, 2499-505. doi:10.1007/s11033-010-0387-5. https://pubmed.ncbi.nlm.nih.gov/21210224/
9. Williams, Jan M, Johnson, Ashley C, Stelloh, Cary, Roman, Richard J, Garrett, Michael R. 2012. Genetic variants in Arhgef11 are associated with kidney injury in the Dahl salt-sensitive rat. In Hypertension (Dallas, Tex. : 1979), 60, 1157-68. doi:10.1161/HYPERTENSIONAHA.112.199240. https://pubmed.ncbi.nlm.nih.gov/22987919/