Nr1h2-flox 基因敲除小鼠

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产品名称

Nr1h2-flox 基因敲除小鼠

产品编号

S-CKO-06550

品系全称

C57BL/6NCya-Nr1h2em1flox/Cya

品系背景

C57BL/6NCya

品系编号

CKOCMP-22260-Nr1h2-B6N-VA

品系状态

使用本品系发表的文献需注明: Nr1h2-flox 基因敲除小鼠 mice (Strain S-CKO-06550) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO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
nuclear receptor subfamily 1, group H, member 2
基因别称
LXR,LXRB,LXRBSV,LXRbeta,NER1,OR-1,RIP15,UR,Unr,Unr2
染色体号
Chr 7 (Mouse)
转录本 ID
NCBI: NM_001285517 | Ensembl: ENSMUST00000073488
修饰方式
条件性基因敲除
靶向范围
Exon 3~7
敲除长度
~2.1 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:1352463Homozygous null mutations cause altered lipid, cholesterol and glucose metabolism and may lead to elevated cartilage matrix catabolism and PGE2 production, lipid-laden uterus myocytes and Sertoli cells, impaired uterus contractility and parturition, and higher susceptibility to bacterial infection.
NR1H2基因,也称为LXRβ(Liver X Receptor beta),是一种位于人类19号染色体的基因。它编码的蛋白是一种核受体,属于LXR(Liver X Receptor)家族,该家族包括LXRα(NR1H3)和LXRβ(NR1H2)。LXR家族成员作为胆固醇传感器,在细胞内调控脂质稳态中发挥着关键作用[6]。NR1H2在多种组织中广泛表达,并在脂质代谢、炎症调节、生殖发育等方面扮演重要角色[6]。

NR1H2基因的变异与多种疾病的发生发展相关。研究显示,NR1H2基因的遗传变异可能与晚发性阿尔茨海默病的发生风险相关[1]。此外,NR1H2基因的变异还与2型糖尿病的发生发展有关。在一项对1574名欧洲血统的2型糖尿病高风险个体的研究中,发现NR1H2基因的两个单核苷酸多态性(SNPs)rs2248949和rs1405655与胰岛素分泌功能相关[2]。在伊朗人群中,NR1H2基因的两个SNPs(rs28514894和rs2303044)被发现与2型糖尿病的发生风险显著相关[3]。

NR1H2基因的变异还与妊娠期高血压疾病(preeclampsia)的发生相关。研究发现,NR1H2基因的一个常见多态性rs2695121与preeclampsia的发生显著相关[4]。此外,NR1H2基因的变异还与抑郁症的发生相关。研究发现,NR1H2基因的变异可能与应激诱导的抑郁症的发生相关,NR1H2基因的变异可能通过影响胆固醇代谢导致神经元突触可塑性的改变,进而参与抑郁症的发生[5]。

NR1H2基因的变异还与男性生育能力相关。研究发现,LXR家族成员在调节正常男性生殖功能的脂质平衡中发挥着重要作用,并且可能与男性不育和脂质代谢紊乱或肥胖有关[6]。此外,NR1H2基因的变异还与自闭症谱系障碍(ASD)的发生相关。研究发现,NR1H2基因的变异可能与ASD的发生相关,并且与oxysterol代谢紊乱有关[7]。

NR1H2基因的变异还与膀胱外翻-尿道上裂复合体(BEEC)的发生相关。研究发现,NR1H2基因的一个新发变异与膀胱外翻的发生相关[8]。此外,NR1H2基因的变异还与性发育障碍(DSD)的发生相关。研究发现,NR1H2基因的变异与NR5A1/SF-1基因的变异相互作用,可能参与了DSD的发生[9]。

综上所述,NR1H2基因是一个重要的核受体基因,参与调控脂质代谢、炎症调节、生殖发育等过程。NR1H2基因的变异与多种疾病的发生发展相关,包括阿尔茨海默病、2型糖尿病、preeclampsia、抑郁症、男性不育、ASD、BEEC和DSD等。NR1H2基因的研究有助于深入理解脂质代谢与这些疾病之间的关系,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Adighibe, Omanma, Arepalli, Sampath, Duckworth, Jaime, Hardy, John, Wavrant-De Vrièze, Fabienne. 2005. Genetic variability at the LXR gene (NR1H2) may contribute to the risk of Alzheimer's disease. In Neurobiology of aging, 27, 1431-4. doi:. https://pubmed.ncbi.nlm.nih.gov/16207502/
2. Ketterer, Caroline, Müssig, Karsten, Machicao, Fausto, Häring, Hans-Ulrich, Staiger, Harald. 2010. Genetic variation within the NR1H2 gene encoding liver X receptor β associates with insulin secretion in subjects at increased risk for type 2 diabetes. In Journal of molecular medicine (Berlin, Germany), 89, 75-81. doi:10.1007/s00109-010-0687-1. https://pubmed.ncbi.nlm.nih.gov/21042792/
3. Sadeghi, Mohammad Bagher, Nakhaee, Alireza, Saravani, Ramin, Sargazi, Saman. 2021. Significant association of LXRβ (NR1H2) polymorphisms (rs28514894, rs2303044) with type 2 diabetes mellitus and laboratory characteristics. In Journal of diabetes and metabolic disorders, 20, 261-270. doi:10.1007/s40200-021-00740-3. https://pubmed.ncbi.nlm.nih.gov/34178836/
4. Mouzat, Kevin, Mercier, Eric, Polge, Anne, Lumbroso, Serge, Gris, Jean-Christophe. 2011. A common polymorphism in NR1H2 (LXRbeta) is associated with preeclampsia. In BMC medical genetics, 12, 145. doi:10.1186/1471-2350-12-145. https://pubmed.ncbi.nlm.nih.gov/22029530/
5. Shi, Rui, Li, Yingmin, Zhu, Weihao, Cong, Bin, Shi, Weibo. 2024. The Regulation of Frontal Cortex Cholesterol Metabolism Abnormalities by NR3C1/NRIP1/NR1H2 Is Involved in the Occurrence of Stress-Induced Depression. In International journal of molecular sciences, 25, . doi:10.3390/ijms25158075. https://pubmed.ncbi.nlm.nih.gov/39125645/
6. Jarvis, Sheba, Williamson, Catherine, Bevan, Charlotte L. 2019. Liver X Receptors and Male (In)fertility. In International journal of molecular sciences, 20, . doi:10.3390/ijms20215379. https://pubmed.ncbi.nlm.nih.gov/31671745/
7. Menteşe Babayiğit, Tuğba, Gümüş-Akay, Güvem, Uytun, Merve Çikili, Yürümez, Esra, Öztop, Didem Behice. 2024. Investigation of Liver X Receptor Gene Variants and Oxysterol Dysregulation in Autism Spectrum Disorder. In Children (Basel, Switzerland), 11, . doi:10.3390/children11050551. https://pubmed.ncbi.nlm.nih.gov/38790546/
8. Köllges, Ricarda, Stegmann, Jil, Schneider, Sophia, Ludwig, Kerstin U, Reutter, Heiko. 2023. Exome Survey and Candidate Gene Re-Sequencing Identifies Novel Exstrophy Candidate Genes and Implicates LZTR1 in Disease Formation. In Biomolecules, 13, . doi:10.3390/biom13071117. https://pubmed.ncbi.nlm.nih.gov/37509153/
9. Naamneh Elzenaty, Rawda, Kouri, Chrysanthi, Martinez de Lapiscina, Idoia, Camats-Tarruella, Núria, Flück, Christa E. 2024. NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor. In International journal of molecular sciences, 25, . doi:10.3390/ijms251810109. https://pubmed.ncbi.nlm.nih.gov/39337600/