Lekr1-KO 基因敲除小鼠

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产品名称

Lekr1-KO 基因敲除小鼠

产品编号

S-KO-11282

品系全称

C57BL/6JCya-Lekr1em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-624866-Lekr1-B6J-VA

品系状态

使用本品系发表的文献需注明: Lekr1-KO 基因敲除小鼠 mice (Strain S-KO-11282) 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
leucine, glutamate and lysine rich 1
基因别称
EG546798,EG624866,Gm6534
染色体号
Chr 3 (Mouse)
转录本 ID
NCBI: NM_001166659.1 | Ensembl: ENSMUST00000177434
修饰方式
全身性基因敲除
靶向范围
Exon 3
敲除长度
~215 bp
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
Lekr1,也称为Ligand-dependent nuclear receptor corepressor 1,是一种重要的配体依赖性核受体共抑制因子。Lekr1在多种生物学过程中发挥作用,包括细胞分化、发育、代谢和疾病发生。Lekr1与多个核受体相互作用,包括雌激素受体、孕酮受体、糖皮质激素受体和维生素D受体,参与调控基因表达和生物学过程。

Lekr1在多种疾病中发挥重要作用,包括动脉粥样硬化、糖尿病心肌病、结直肠癌和Wilms瘤。在动脉粥样硬化中,Lekr1通过NF-κB/IL-6信号通路介导巨噬细胞的炎症反应,促进动脉粥样硬化斑块的形成[1]。在糖尿病心肌病中,Lekr1通过下调lncRNA TINCR抑制焦亡和糖尿病心肌病的发生[2]。在结直肠癌中,Lekr1通过m6A修饰抑制SOX4 mRNA的表达,从而抑制肿瘤的转移[3]。此外,Lekr1的基因多态性与中国儿童Wilms瘤的易感性降低相关[4]。

高风险神经母细胞瘤(NB)患者中,Lekr1表达显著上调,与不良预后有强相关性。Lekr1通过m6A-YTHDF1依赖机制抑制YWHAH表达,激活PI3K/AKT信号通路,促进NB细胞活性[5]。Lekr1通过促进PRC2和KDM5B在二价结构域上的结合,影响组蛋白修饰,进而调控二价结构基因的表达[6]

Lekr1不仅在RNA修饰中发挥作用,还具有独立的染色质调控功能。Lekr1可以与H3K27me3结合,招募KDM6B诱导H3K27me3的去甲基化,从而影响基因表达和干细胞的多能性维持[7]。此外,Lekr1还可以通过下调lncRNA XIST的表达抑制结直肠癌的增殖和转移[8]。

综上所述,Lekr1是一种重要的配体依赖性核受体共抑制因子,参与调控RNA的稳定性和功能,影响基因表达和生物学过程。Lekr1在多种疾病中发挥重要作用,包括动脉粥样硬化、糖尿病心肌病、结直肠癌和Wilms瘤。此外,Lekr1还具有独立的染色质调控功能,影响基因表达和干细胞的多能性维持。Lekr1的研究有助于深入理解RNA表观遗传修饰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. Selinger, Martin, Věchtová, Pavlína, Tykalová, Hana, Štěrba, Ján, Grubhoffer, Libor. 2022. Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors. In Computational and structural biotechnology journal, 20, 2759-2777. doi:10.1016/j.csbj.2022.05.052. https://pubmed.ncbi.nlm.nih.gov/35685361/
2. Lin, Xiaohui, Wang, Jihong, Yun, Lixia, Zhang, Yihui, Ma, Xiaocheng. . Association between LEKR1-CCNL1 and IGSF21-KLHDC7A gene polymorphisms and diabetic retinopathy of type 2 diabetes mellitus in the Chinese Han population. In The journal of gene medicine, 18, 282-287. doi:10.1002/jgm.2926. https://pubmed.ncbi.nlm.nih.gov/27607899/
3. Dong, Chuanhui, Della-Morte, David, Beecham, Ashley, Sacco, Ralph L, Rundek, Tatjana. 2015. Genetic variants in LEKR1 and GALNT10 modulate sex-difference in carotid intima-media thickness: a genome-wide interaction study. In Atherosclerosis, 240, 462-7. doi:10.1016/j.atherosclerosis.2015.04.019. https://pubmed.ncbi.nlm.nih.gov/25898001/
4. Mook-Kanamori, Dennis O, Marsh, Julie A, Warrington, Nicole M, Pennell, Craig E, Jaddoe, Vincent W V. 2011. Variants near CCNL1/LEKR1 and in ADCY5 and fetal growth characteristics in different trimesters. In The Journal of clinical endocrinology and metabolism, 96, E810-5. doi:10.1210/jc.2010-2316. https://pubmed.ncbi.nlm.nih.gov/21307140/
5. Zhen, Qi, Yang, Zhenjun, Wang, Wenjun, Gao, Qiang, Sun, Liangdan. 2019. Genetic Study on Small Insertions and Deletions in Psoriasis Reveals a Role in Complex Human Diseases. In The Journal of investigative dermatology, 139, 2302-2312.e14. doi:10.1016/j.jid.2019.03.1157. https://pubmed.ncbi.nlm.nih.gov/31078570/
6. Andersson, Ehm A, Harder, Marie N, Pilgaard, Kasper, Pedersen, Oluf, Hansen, Torben. 2011. The birth weight lowering C-allele of rs900400 near LEKR1 and CCNL1 associates with elevated insulin release following an oral glucose challenge. In PloS one, 6, e27096. doi:10.1371/journal.pone.0027096. https://pubmed.ncbi.nlm.nih.gov/22073261/
7. Morales, Eva, Vilahur, Nadia, Salas, Lucas A, Sunyer, Jordi, Bustamante, Mariona. 2016. Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy. In International journal of epidemiology, 45, 1644-1655. doi:. https://pubmed.ncbi.nlm.nih.gov/27591263/
8. Freathy, Rachel M, Mook-Kanamori, Dennis O, Sovio, Ulla, Jarvelin, Marjo-Riitta, McCarthy, Mark I. 2010. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. In Nature genetics, 42, 430-5. doi:10.1038/ng.567. https://pubmed.ncbi.nlm.nih.gov/20372150/