Alpk1-KO 基因敲除小鼠

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产品名称

Alpk1-KO 基因敲除小鼠

产品编号

S-KO-13579

品系全称

C57BL/6JCya-Alpk1em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-71481-Alpk1-B6J-VA

品系状态

使用本品系发表的文献需注明: Alpk1-KO 基因敲除小鼠 mice (Strain S-KO-13579) 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
alpha-kinase 1
基因别称
8430410J10Rik,LAK
染色体号
Chr 3 (Mouse)
转录本 ID
NCBI: NM_027808 | Ensembl: ENSMUST00000029662
修饰方式
全身性基因敲除
靶向范围
Exon 5~14
敲除长度
~17.3 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:1918731Homozygosity for the p.T237M mutation leads to increased levels of certain chemokines.
ALPK1,全称为Alpha-kinase 1,是一种非典型的蛋白激酶,在哺乳动物细胞中广泛表达。ALPK1的主要功能是作为胞质内的先天免疫受体,识别并结合细菌代谢产物ADP-β-D-甘露庚糖(ADP-Hep),进而激活NF-κB信号通路,从而触发宿主对细菌感染的免疫反应[6]。此外,ALPK1还能够磷酸化TIFA(TRAF-interacting protein with forkhead-associated domain),进而激活免疫信号通路[6]。

ALPK1基因的突变与多种疾病相关。例如,ALPK1基因的p.Thr237Met和p.Tyr254Cys突变会导致ROSAH(retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache)综合征,这是一种以视网膜变性、视神经水肿、脾肿大、无汗症和头痛为特征的自身炎症性疾病[1]。此外,ALPK1基因的p.V1092A突变会导致螺旋腺瘤和螺旋腺癌,这两种疾病都与皮肤腺体的肿瘤形成有关[3]。此外,ALPK1基因的罕见错义变异体还可能增加儿童周期性发热、口腔溃疡、咽炎和腺炎(PFAPA)综合征的风险[4]。

除了自身炎症性疾病,ALPK1还与糖尿病肾病有关。研究发现,ALPK1在糖尿病肾病中通过促进IL-1β的产生,进而促进肾纤维化[2]。此外,ALPK1还与痛风相关。研究发现,痛风患者外周血白细胞中的ALPK1基因表达显著增加[5]。

除了上述疾病,ALPK1还与结直肠癌和颞下颌关节滑膜炎有关。研究发现,Fusobacterium nucleatum释放的ADP-heptose能够通过激活ALPK1/TIFA/TRAF6通路,促进结直肠癌的发生[7]。此外,研究发现,ALPK1在颞下颌关节滑膜炎中高表达,并能够促进M1巨噬细胞的极化,从而加剧炎症反应[8]。

综上所述,ALPK1是一种重要的非典型蛋白激酶,参与宿主对细菌感染的免疫反应,并与其他多种疾病相关。ALPK1的突变和表达异常可能与自身炎症性疾病、糖尿病肾病、痛风、结直肠癌和颞下颌关节滑膜炎等疾病的发生和发展密切相关。因此,研究ALPK1的生物学功能和作用机制,有助于深入理解这些疾病的发病机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Kozycki, Christina Torres, Kodati, Shilpa, Huryn, Laryssa, Aksentijevich, Ivona, Kastner, Daniel L. 2022. Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome. In Annals of the rheumatic diseases, 81, 1453-1464. doi:10.1136/annrheumdis-2022-222629. https://pubmed.ncbi.nlm.nih.gov/35868845/
2. Cui, Xinyuan, Li, Yifu, Yuan, Shuguang, Liu, Hong, Zhu, Xuejing. 2023. Alpha-kinase1 promotes tubular injury and interstitial inflammation in diabetic nephropathy by canonical pyroptosis pathway. In Biological research, 56, 5. doi:10.1186/s40659-023-00416-7. https://pubmed.ncbi.nlm.nih.gov/36732854/
3. Snelling, Tom, Saalfrank, Anton, Wood, Nicola T, Cohen, Philip. 2023. ALPK1 mutants causing ROSAH syndrome or Spiradenoma are activated by human nucleotide sugars. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2313148120. doi:10.1073/pnas.2313148120. https://pubmed.ncbi.nlm.nih.gov/38060563/
4. Sangiorgi, Eugenio, Azzarà, Alessia, Molinario, Clelia, Gurrieri, Fiorella, Manna, Raffaele. 2019. Rare missense variants in the ALPK1 gene may predispose to periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. In European journal of human genetics : EJHG, 27, 1361-1368. doi:10.1038/s41431-019-0421-6. https://pubmed.ncbi.nlm.nih.gov/31053777/
5. Natsuko, Paniagua-Díaz, Laura, Sanchez-Chapul, Denise, Clavijo-Cornejo, Fausto, Sanchez-Muñoz, Ambar, López-Macay. 2022. Differential gene expression of ABCG2, SLC22A12, IL-1β, and ALPK1 in peripheral blood leukocytes of primary gout patients with hyperuricemia and their comorbidities: a case-control study. In European journal of medical research, 27, 62. doi:10.1186/s40001-022-00684-1. https://pubmed.ncbi.nlm.nih.gov/35505381/
6. Zhou, Ping, She, Yang, Dong, Na, Zamyatina, Alla, Shao, Feng. 2018. Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose. In Nature, 561, 122-126. doi:10.1038/s41586-018-0433-3. https://pubmed.ncbi.nlm.nih.gov/30111836/
7. Martin-Gallausiaux, Camille, Salesse, Laurène, Garcia-Weber, Diego, Arrieumerlou, Cécile, Lapaque, Nicolas. 2023. Fusobacterium nucleatum promotes inflammatory and anti-apoptotic responses in colorectal cancer cells via ADP-heptose release and ALPK1/TIFA axis activation. In Gut microbes, 16, 2295384. doi:10.1080/19490976.2023.2295384. https://pubmed.ncbi.nlm.nih.gov/38126163/
8. Zhao, Jie, Feng, Yaping, Liu, Xin, Ke, Jin, Long, Xing. . The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis. In Journal of cellular and molecular medicine, 28, e18172. doi:10.1111/jcmm.18172. https://pubmed.ncbi.nlm.nih.gov/38494837/