Esrra-KO 基因敲除小鼠

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产品名称

Esrra-KO 基因敲除小鼠

产品编号

S-KO-08470

品系全称

C57BL/6NCya-Esrraem1/Cya

品系背景

C57BL/6NCya

品系编号

KOCMP-26379-Esrra-B6N-VA

品系状态

使用本品系发表的文献需注明: Esrra-KO 基因敲除小鼠 mice (Strain S-KO-08470) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
KO小鼠库模型
核受体Brite

基本信息

基因研究概述

质控标准

基因
基因全称
estrogen related receptor, alpha
基因别称
ERRalpha,Err1,Estrra,Nr3b1
染色体号
Chr 19 (Mouse)
转录本 ID
NCBI: NM_007953 | Ensembl: ENSMUST00000025906
修饰方式
全身性基因敲除
靶向范围
Exon 2
敲除长度
~1.5 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:1346831Homozygous mice for one mutation were viable but showed reduced weight gain associated with decreased peripheral fat deposition. Mutant mice were resistant to high-fat diet induced obesity. Another targeted mutation resulted in no significant abnormalities in homozygotes.
基因ESRRa,也称为雌激素相关受体α,是一种孤儿核受体,属于核激素受体超家族。ESRRa是一种配体非依赖性的转录因子,主要表达于高代谢器官,如肾脏、肠道、心脏和肝脏等。ESRRa通过结合特定的DNA序列,调控下游基因的表达,影响细胞的代谢、分化和炎症反应等生物学过程。

ESRRa在多种疾病中发挥重要作用,包括肾脏病、肠炎、卵巢癌、胃癌和非酒精性脂肪性肝炎等。例如,在肾脏病中,ESRRa通过调节代谢和分化,保护肾脏免受损伤[1]。在肠炎中,ESRRa通过激活自噬流和调节肠道菌群,维持肠道稳态[2]。在卵巢癌中,ESRRa与C11orf20基因融合,可能参与卵巢癌的发生发展[3]。在胃癌中,ESRRa通过调节CDC25C/CDK1/CyclinB1信号通路,促进胃癌细胞的增殖和侵袭[4]。在非酒精性脂肪性肝炎中,ESRRa通过调节Rplp1介导的蛋白质翻译,影响自噬和溶酶体功能,参与疾病的发生发展[6]。

研究表明,ESRRa的调控机制复杂多样。例如,在心脏发育中,组蛋白去甲基化酶KDM5通过促进脂肪酸氧化、氧化磷酸化和肌节组织,促进心肌细胞的成熟[7]。在巨噬细胞中,AMPK和SIRT1激活ESRRa的表达,进而激活自噬相关基因的表达,促进巨噬细胞的抗菌防御[8]。此外,EMPAGLIFLOZIN通过上调ESRRa的表达,改善糖尿病肾脏损伤[5]。

综上所述,ESRRa是一种重要的核受体,通过调控代谢、分化和炎症反应等生物学过程,在多种疾病中发挥重要作用。ESRRa的调控机制复杂多样,涉及多种信号通路和转录因子。ESRRa的研究有助于深入理解核受体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. Dhillon, Poonam, Park, Jihwan, Hurtado Del Pozo, Carmen, Montserrat, Nuria, Susztak, Katalin. 2020. The Nuclear Receptor ESRRA Protects from Kidney Disease by Coupling Metabolism and Differentiation. In Cell metabolism, 33, 379-394.e8. doi:10.1016/j.cmet.2020.11.011. https://pubmed.ncbi.nlm.nih.gov/33301705/
2. Kim, Sup, Lee, June-Young, Shin, Seul Gi, Bae, Jin-Woo, Jo, Eun-Kyeong. 2020. ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota. In Autophagy, 17, 2856-2875. doi:10.1080/15548627.2020.1847460. https://pubmed.ncbi.nlm.nih.gov/33172329/
3. Micci, Francesca, Panagopoulos, Ioannis, Thorsen, Jim, Tropé, Claes Gøran, Heim, Sverre. 2014. Low frequency of ESRRA-C11orf20 fusion gene in ovarian carcinomas. In PLoS biology, 12, e1001784. doi:10.1371/journal.pbio.1001784. https://pubmed.ncbi.nlm.nih.gov/24504521/
4. Li, Feng-Nan, Zhang, Qin-Yi, Li, Ou, Shu, Yi-Jun, Dong, Ping. 2021. ESRRA promotes gastric cancer development by regulating the CDC25C/CDK1/CyclinB1 pathway via DSN1. In International journal of biological sciences, 17, 1909-1924. doi:10.7150/ijbs.57623. https://pubmed.ncbi.nlm.nih.gov/34131395/
5. Yang, Keju, Liang, Wei, Hu, Hongtu, Chen, Zhaowei, Ding, Guohua. 2024. ESRRA modulation by empagliflozin mitigates diabetic tubular injury via mitochondrial restoration. In Cellular signalling, 122, 111308. doi:10.1016/j.cellsig.2024.111308. https://pubmed.ncbi.nlm.nih.gov/39059756/
6. Tripathi, Madhulika, Gauthier, Karine, Sandireddy, Reddemma, Yen, Paul M, Singh, Brijesh K. 2024. Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in metabolic dysfunction-associated steatohepatitis and reversed by alternate day fasting. In Molecular metabolism, 87, 101997. doi:10.1016/j.molmet.2024.101997. https://pubmed.ncbi.nlm.nih.gov/39032642/
7. Deogharia, Manisha, Venegas-Zamora, Leslye, Agrawal, Akanksha, Marian, Ali J, Gurha, Priyatansh. . Histone demethylase KDM5 regulates cardiomyocyte maturation by promoting fatty acid oxidation, oxidative phosphorylation, and myofibrillar organization. In Cardiovascular research, 120, 630-643. doi:10.1093/cvr/cvae014. https://pubmed.ncbi.nlm.nih.gov/38230606/
8. Kim, Soo Yeon, Yang, Chul-Su, Lee, Hye-Mi, Giguère, Vincent, Jo, Eun-Kyeong. 2017. ESRRA (estrogen-related receptor α) is a key coordinator of transcriptional and post-translational activation of autophagy to promote innate host defense. In Autophagy, 14, 152-168. doi:10.1080/15548627.2017.1339001. https://pubmed.ncbi.nlm.nih.gov/28841353/