Ahr-flox 基因敲除小鼠

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产品名称

Ahr-flox 基因敲除小鼠

产品编号

S-CKO-01108

品系全称

C57BL/6NCya-Ahrem1flox/Cya

品系背景

C57BL/6NCya

品系编号

CKOCMP-11622-Ahr-B6N-VA

品系状态

使用本品系发表的文献需注明: Ahr-flox 基因敲除小鼠 mice (Strain S-CKO-01108) 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
aryl-hydrocarbon receptor
基因别称
Ah,Ahh,Ahre,In,bHLHe76
染色体号
Chr 12 (Mouse)
转录本 ID
NCBI: NM_013464 | Ensembl: ENSMUST00000116436
修饰方式
条件性基因敲除
靶向范围
Exon 5~7
敲除长度
~3.8 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:105043Homozygotes for null or hypomorphic alleles do not respond to cyclic compounds (e.g., dioxin) and are resistant to their teratogenic effects. Depending on the allele, null mutants may also have liver defects, impaired female fertility, neonatal or postnatal lethality, and spleen abnormalities. Conditional homozygous KO in the retina leads to retinal degeneration. Conditional KO in neural progenitor cells leads to decreased susceptibility to ischemic brain injury.

发表文献

npj Regenerative Medicine
2023-11-07
Aryl hydrocarbon receptor regulates IL-22 receptor expression on thymic epithelial cell and accelerates thymus regeneration
1
Ahr基因编码芳烃受体(aryl hydrocarbon receptor, AhR),是一种配体激活的转录因子,在哺乳动物中负责介导对二噁英及其相关化合物的反应。AhR通过与特定的配体结合而被激活,从而诱导下游基因的表达,这些基因参与解毒、细胞代谢、免疫反应等多种生物学过程。AhR的表达具有组织特异性和发育特异性,其在脂肪分化过程中会被下调,导致对异生物质的反应能力下降[7]。AhR基因的启动子区富含GC盒,缺乏TATA或CCAAT盒,并包含多个转录因子结合位点,如Sp1、cAMP反应元件、AP-1和E盒等[9]。

AhR基因的表达受到多种因素的调控。研究发现,AhR基因的启动子区存在一个抑制区域,该区域在脂肪分化过程中会抑制AhR基因的转录活性[7]。此外,AhR基因的表达还受到组蛋白乙酰化水平的调控,n-丁酸等组蛋白去乙酰化酶抑制剂可以增强AhR基因启动子的活性[5]。此外,AhR基因的表达还受到其他转录因子的调控,如AhR可以与ARNT、CREB、E4F、Sp1、ZBED1、JunB、c-Rel和NF-κB等转录因子相互作用,共同调控AhR基因的表达[6]。

AhR基因的突变或表达异常与多种疾病的发生发展密切相关。研究发现,AhR基因的突变或表达异常可以导致对二噁英等异生物质的敏感性增加,从而增加患癌症、免疫性疾病等疾病的风险[1]。此外,AhR基因的表达还与脂肪代谢、糖尿病、动脉粥样硬化等疾病的发生发展密切相关[2,3]。AhR基因的表达还受到其他因素的调控,如AhR可以与SPHK2相互作用,影响AhR的核定位和下游基因的表达[4]。此外,AhR基因的表达还受到缺氧等环境因素的影响,AhR基因启动子区存在一个急性缺氧反应元件,可以驱动报告基因在缺氧条件下的表达[8]。

综上所述,AhR基因是一种重要的转录因子,参与调控多种生物学过程。AhR基因的表达受到多种因素的调控,包括启动子区的抑制区域、组蛋白乙酰化水平、转录因子相互作用和环境因素等。AhR基因的突变或表达异常与多种疾病的发生发展密切相关。AhR基因的研究有助于深入理解AhR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. Ferraù, F, Romeo, P D, Puglisi, S, Picerno, I A M, Cannavò, S. 2018. GSTP1 gene methylation and AHR rs2066853 variant predict resistance to first generation somatostatin analogs in patients with acromegaly. In Journal of endocrinological investigation, 42, 825-831. doi:10.1007/s40618-018-0988-8. https://pubmed.ncbi.nlm.nih.gov/30488289/
2. Saito, Nao, Kanno, Yuichiro, Yamashita, Naoya, Yoshinari, Kouichi, Nemoto, Kiyomitsu. . The Differential Selectivity of Aryl Hydrocarbon Receptor (AHR) Agonists towards AHR-Dependent Suppression of Mammosphere Formation and Gene Transcription in Human Breast Cancer Cells. In Biological & pharmaceutical bulletin, 44, 571-578. doi:10.1248/bpb.b20-00961. https://pubmed.ncbi.nlm.nih.gov/33790107/
3. Yokoyama, Shigetoshi, Koo, Imhoi, Aibara, Daisuke, Perdew, Gary H, Patterson, Andrew D. 2024. Sphingosine Kinase 2 Regulates Aryl Hydrocarbon Receptor Nuclear Translocation and Target Gene Activation. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2400794. doi:10.1002/advs.202400794. https://pubmed.ncbi.nlm.nih.gov/39207053/
4. Landi, Claudia, Liberatori, Giulia, Puccini, Monica, Corsi, Ilaria, Bini, Luca. 2023. Proteomics coupled with AhR-reporter gene bioassay for human and environmental safety assessment of sewage sludge and hydrochar. In The Science of the total environment, 891, 164651. doi:10.1016/j.scitotenv.2023.164651. https://pubmed.ncbi.nlm.nih.gov/37277040/
5. Garrison, P M, Denison, M S. . Analysis of the murine AhR gene promoter. In Journal of biochemical and molecular toxicology, 14, 1-10. doi:. https://pubmed.ncbi.nlm.nih.gov/10561076/
6. Johari, Yusuf B, Scarrott, Joseph M, Pohle, Thilo H, Brown, Adam J, James, David C. 2022. Engineering of the CMV promoter for controlled expression of recombinant genes in HEK293 cells. In Biotechnology journal, 17, e2200062. doi:10.1002/biot.202200062. https://pubmed.ncbi.nlm.nih.gov/35482470/
7. Shimba, Shigeki, Hayashi, Mitsuaki, Ohno, Toshiharu, Tezuka, Masakatsu. . Transcriptional regulation of the AhR gene during adipose differentiation. In Biological & pharmaceutical bulletin, 26, 1266-71. doi:. https://pubmed.ncbi.nlm.nih.gov/12951469/
8. Cilek, Mehmet Zeynel, Hirohata, Satoshi, Faruk Hatipoglu, Omer, Kusachi, Shozo, Ninomiya, Yoshifumi. . AHR, a novel acute hypoxia-response sequence, drives reporter gene expression under hypoxia in vitro and in vivo. In Cell biology international, 35, 1-8. doi:10.1042/CBI20100290. https://pubmed.ncbi.nlm.nih.gov/20795945/
9. Schmidt, J V, Carver, L A, Bradfield, C A. . Molecular characterization of the murine Ahr gene. Organization, promoter analysis, and chromosomal assignment. In The Journal of biological chemistry, 268, 22203-9. doi:. https://pubmed.ncbi.nlm.nih.gov/8408082/

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