C57BL/6JCya-Alpk1em1flox/Cya
Common Name:
Alpk1-flox
Product ID:
S-CKO-15084
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Alpk1-flox
Strain ID
CKOCMP-71481-Alpk1-B6J-VA
Gene Name
Product ID
S-CKO-15084
Gene Alias
8430410J10Rik; LAK
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
3
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Alpk1em1flox/Cya mice (Catalog S-CKO-15084) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000029662
NCBI RefSeq
NM_027808
Target Region
Exon 3
Size of Effective Region
~1.4 kb
Detailed Document
Overview of Gene Research
Alpk1, an atypical protein kinase, is a pattern recognition receptor (PRR) that activates the NF-κB pathway, playing a crucial role in innate immunity [3,4,5,6]. It is activated by the bacterial nucleotide sugar ADP-heptose and phosphorylates TIFA to initiate a signaling pathway against microbial infection [2].
In ROSAH syndrome, gain-of-function mutations in ALPK1 lead to an NF-κB-mediated autoinflammatory disease, with patients showing various inflammatory features [1]. Alpk1 knock-in mice with the T237M mutation exhibit subclinical inflammation, demonstrating its role in this autoinflammatory disease [1].
In colorectal cancer, Fusobacterium nucleatum promotes cancer cell adhesion to endothelial cells and metastasis by inducing the ALPK1/NF-κB/ICAM1 axis. High ALPK1 expression in patients is associated with shorter survival times [3].
In hepatitis B models, the ALPK1 agonist DF-006 shows anti-HBV efficacy, reducing viral markers and upregulating NF-κB-targeted genes involved in innate immunity [4].
In osteoarthritis (OA) mouse models, elevation of ALPK1 in degraded cartilage is observed. Intra-articular administration of recombinant human ALPK1 exacerbates OA, while ALPK1 knockout reverses this process, indicating ALPK1 accelerates OA pathogenesis by activating NLRP3 signaling [7].
In temporomandibular joint osteoarthritis (TMJOA) mouse models, ALPK1 knockout mice have attenuated cartilage and subchondral bone damage, as well as synovitis, compared to wild-type mice, suggesting ALPK1 exacerbates TMJOA cartilage degradation through the NF-κB and ERK1/2 signaling pathways [8].
In streptozotocin-induced nephropathy, high glucose increases ALPK1 levels, and elevated ALPK1 enhances renal CCL2 and CCL5 expressions, suggesting ALPK1 is a mediator in diabetic nephropathies induction [9].
In conclusion, Alpk1 is a key regulator in the NF-κB-related immune signaling pathway. Its gain-of-function mutations cause autoinflammatory diseases like ROSAH syndrome. In various disease models, Alpk1 has been shown to play significant roles in promoting disease progression, such as in cancer metastasis, viral infection, and degenerative joint diseases. Gene knockout and knock-in mouse models have been instrumental in revealing these functions, providing insights into the underlying disease mechanisms and potential therapeutic targets.
References:
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. 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/
3. Zhang, Ying, Zhang, Lu, Zheng, Sheng, Si, Jianmin, Zhuo, Wei. . Fusobacterium nucleatum promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis. In Gut microbes, 14, 2038852. doi:10.1080/19490976.2022.2038852. https://pubmed.ncbi.nlm.nih.gov/35220887/
4. Xu, Cong, Fan, Jieqing, Liu, Danyang, Lichenstein, Henri, Xu, Tian. 2022. Alpha-kinase 1 (ALPK1) agonist DF-006 demonstrates potent efficacy in mouse and primary human hepatocyte (PHH) models of hepatitis B. In Hepatology (Baltimore, Md.), 77, 275-289. doi:10.1002/hep.32614. https://pubmed.ncbi.nlm.nih.gov/35699669/
5. Lu, Jing, Liu, Xue, Li, Xinghua, Sun, Hongzhe, Yang, Xinming. 2024. Copper regulates the host innate immune response against bacterial infection via activation of ALPK1 kinase. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2311630121. doi:10.1073/pnas.2311630121. https://pubmed.ncbi.nlm.nih.gov/38232278/
6. 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/
7. Liu, Xin, Zhao, Jie, Jiang, Henghua, Ke, Jin, Long, Xing. 2022. ALPK1 Accelerates the Pathogenesis of Osteoarthritis by Activating NLRP3 Signaling. In Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 37, 1973-1985. doi:10.1002/jbmr.4669. https://pubmed.ncbi.nlm.nih.gov/36053817/
8. Liu, X, Zhao, J, Jiang, H, Ke, J, Long, X. 2022. ALPK1 Aggravates TMJOA Cartilage Degradation via NF-κB and ERK1/2 Signaling. In Journal of dental research, 101, 1499-1509. doi:10.1177/00220345221100179. https://pubmed.ncbi.nlm.nih.gov/35689396/
9. Lee, Chi-Pin, Nithiyanantham, Srinivasan, Hsu, Hui-Ting, Kuo, Tzer-Min, Ko, Ying-Chin. 2019. ALPK1 regulates streptozotocin-induced nephropathy through CCL2 and CCL5 expressions. In Journal of cellular and molecular medicine, 23, 7699-7708. doi:10.1111/jcmm.14643. https://pubmed.ncbi.nlm.nih.gov/31557402/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen