Lacc1-flox 基因敲除小鼠

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产品名称

Lacc1-flox 基因敲除小鼠

产品编号

S-CKO-05551

品系全称

C57BL/6JCya-Lacc1em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-210808-Lacc1-B6J-VA

品系状态

使用本品系发表的文献需注明: Lacc1-flox 基因敲除小鼠 mice (Strain S-CKO-05551) 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
laccase domain containing 1
基因别称
9030625A04Rik
染色体号
Chr 14 (Mouse)
转录本 ID
NCBI: NM_172488 | Ensembl: ENSMUST00000062789
修饰方式
条件性基因敲除
靶向范围
Exon 4
敲除长度
~0.8 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:2445077Mice homozygous for a knock-out allele exhibit decreased fatty acid oxidation and glycolysis in macrophages and increased susceptibility to LPS-induced endotoxin shock.
LACC1(Laccase domain containing 1)基因编码一种多铜氧化还原酶,属于laccase家族。LACC1基因的突变与多种炎症性肠病和自身免疫性疾病相关,包括克罗恩病、麻风病、系统性红斑狼疮和幼年特发性关节炎等。LACC1基因的功能目前尚不完全清楚,但研究显示,它可能参与脂肪酸氧化、炎症体激活、活性氧的产生以及巨噬细胞的抗菌反应等生物学过程。此外,LACC1基因的表达在免疫细胞中具有重要作用,尤其是在巨噬细胞和树突状细胞中,其表达水平较高。

研究表明,LACC1基因的突变与炎症性肠病和幼年特发性关节炎的风险增加相关。在LACC1基因敲除小鼠模型中,小鼠表现出更严重的结肠炎和关节炎症状,血清和局部TNF水平显著升高,IL-17A产生CD4+ T细胞的百分比也升高。这些数据提供了关于LACC1在调节炎症过程中TNF和IL-17功能的新见解。这些发现表明,LACC1基因的变异可能通过影响TNF和IL-17的产生,从而在炎症性肠病和自身免疫性疾病中发挥重要作用[1,2,3,4,5,6,7,8,9,10]。

研究发现,LACC1基因的表达在免疫细胞中具有重要作用,尤其是在巨噬细胞和树突状细胞中,其表达水平较高。LACC1基因的突变导致幼年特发性关节炎,其临床表现多样,包括早期对称性和慢性关节炎,以及炎症指标升高。患者血清中IL-6水平显著升高,IFN评分也较高。此外,LACC1基因的变异还与贫血相关,这可能表明LACC1在调节炎症信号通路中发挥重要作用。JAK抑制剂与托珠单抗联合治疗对LACC1基因突变引起的幼年特发性关节炎和贫血患者有效,这为治疗这些疾病提供了新的思路。

综上所述,LACC1基因在炎症性肠病和自身免疫性疾病中发挥重要作用,其突变与疾病风险增加相关。LACC1基因的表达在免疫细胞中具有重要作用,尤其在巨噬细胞和树突状细胞中。LACC1基因的变异导致幼年特发性关节炎和贫血,这可能表明LACC1在调节炎症信号通路中发挥重要作用。JAK抑制剂与托珠单抗联合治疗对LACC1基因突变引起的幼年特发性关节炎和贫血患者有效,这为治疗这些疾病提供了新的思路。

参考文献:
1. Singh, Ankita, Suri, Deepti, Vignesh, Pandiarajan, Jacob, Prince, Girisha, Katta M. 2019. LACC1 gene mutation in three sisters with polyarthritis without systemic features. In Annals of the rheumatic diseases, 79, 425-426. doi:10.1136/annrheumdis-2019-216263. https://pubmed.ncbi.nlm.nih.gov/31811059/
2. Karacan, Ilker, Uğurlu, Serdal, Şahin, Sezgin, Özdoğan, Huri, Turanli, Eda Tahir. . LACC1 Gene Defects in Familial Form of Juvenile Arthritis. In The Journal of rheumatology, 45, 726-728. doi:10.3899/jrheum.170834. https://pubmed.ncbi.nlm.nih.gov/29717096/
3. Kang, Jung-Woo, Yan, Jie, Ranjan, Kishu, Turner, Jerrold R, Abraham, Clara. 2020. Myeloid Cell Expression of LACC1 Is Required for Bacterial Clearance and Control of Intestinal Inflammation. In Gastroenterology, 159, 1051-1067. doi:10.1053/j.gastro.2020.07.024. https://pubmed.ncbi.nlm.nih.gov/32693188/
4. Assadi, Ghazaleh, Vesterlund, Liselotte, Bonfiglio, Ferdinando, Halfvarson, Jonas, D'Amato, Mauro. 2016. Functional Analyses of the Crohn's Disease Risk Gene LACC1. In PloS one, 11, e0168276. doi:10.1371/journal.pone.0168276. https://pubmed.ncbi.nlm.nih.gov/27959965/
5. Zhang, Y, Sun, L N, Yuan, D Y, Zhang, L, Zhang, Y P. . [A case of juvenile arthritis associated with LACC1 gene variation]. In Zhonghua er ke za zhi = Chinese journal of pediatrics, 61, 1048-1050. doi:10.3760/cma.j.cn112140-20230415-00272. https://pubmed.ncbi.nlm.nih.gov/37899347/
6. Assadi, G, Saleh, R, Hadizadeh, F, Sundberg, E, D'Amato, M. 2016. LACC1 polymorphisms in inflammatory bowel disease and juvenile idiopathic arthritis. In Genes and immunity, 17, 261-4. doi:10.1038/gene.2016.17. https://pubmed.ncbi.nlm.nih.gov/27098602/
7. Wu, Yali, Wang, Shasha, Yin, Wen, Yin, Wei, Ding, Yan. 2023. Clinical characteristics and genotype analysis of a Chinese patient with juvenile arthritis due to novel LACC1 frameshift mutation and literature review. In Molecular genetics & genomic medicine, 11, e2175. doi:10.1002/mgg3.2175. https://pubmed.ncbi.nlm.nih.gov/37186377/
8. Rabionet, Raquel, Remesal, Agustín, Mensa-Vilaró, Anna, Estivill, Xavier, Arostegui, Juan I. 2019. Biallelic loss-of-function LACC1/FAMIN Mutations Presenting as Rheumatoid Factor-Negative Polyarticular Juvenile Idiopathic Arthritis. In Scientific reports, 9, 4579. doi:10.1038/s41598-019-40874-2. https://pubmed.ncbi.nlm.nih.gov/30872671/
9. Skon-Hegg, Cara, Zhang, Juan, Wu, Xiumin, Lee, Wyne P, Behrens, Timothy W. 2018. LACC1 Regulates TNF and IL-17 in Mouse Models of Arthritis and Inflammation. In Journal of immunology (Baltimore, Md. : 1950), 202, 183-193. doi:10.4049/jimmunol.1800636. https://pubmed.ncbi.nlm.nih.gov/30510070/
10. He, Tingyan, Wang, Linlin, Huang, Xiaomei, Weng, Ruohang, Yang, Jun. 2024. LACC1 deficiency leading to juvenile arthritis and anemia. In Clinical immunology (Orlando, Fla.), 265, 110290. doi:10.1016/j.clim.2024.110290. https://pubmed.ncbi.nlm.nih.gov/38944365/