C57BL/6NCya-Pmvkem1/Cya
Common Name:
Pmvk-KO
Product ID:
S-KO-12768
Background:
C57BL/6NCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Pmvk-KO
Strain ID
KOCMP-68603-Pmvk-B6N-VA
Gene Name
Product ID
S-KO-12768
Gene Alias
1110011E12Rik; 2900002L22Rik; PMK; PMKA; PMKASE
Background
C57BL/6NCya
NCBI ID
Modification
Conventional knockout
Chromosome
3
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6NCya-Pmvkem1/Cya mice (Catalog S-KO-12768) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000029564
NCBI RefSeq
NM_026784
Target Region
Exon 1~5
Size of Effective Region
~9.9 kb
Detailed Document
Overview of Gene Research
PMVK, short for phosphomevalonate kinase, is an enzyme that catalyzes the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate in the mevalonate pathway. This pathway is crucial for the synthesis of cholesterol and isoprenoid compounds, which play essential roles in cell membrane structure, protein prenylation, and cell signaling [3,5,6].
In lung cancer cells, knockdown of PMVK significantly decreased cell viability and survival fraction after radiotherapy, increased apoptosis, DNA damage, and G2/M phase arrest, and enhanced radiosensitivity by inhibiting the homologous recombination DNA repair pathway via downregulation of replication protein A1 (RPA1) through the ubiquitin-proteasome system. A stable shRNA PMVK mouse xenograft model verified these radiosensitizing effects in vivo [1].
In hepatocellular carcinoma (HCC), depletion of PMVK facilitated CD8+ T cell activation and suppression of tumor growth. PMVK phosphorylates and stabilizes glutamate decarboxylase 1 (GAD1), increasing the synthesis of γ-aminobutyric acid (GABA), which is then converted to 4-acetaminobutyric acid (4-Ac-GABA) and released into the tumor microenvironment to suppress CD8+ T cell activation. Inhibiting PMVK in HCC mouse models overcame resistance to anti-PD-1 immune checkpoint therapy [2].
Also, in a mouse model, deletion of PMVK impaired embryonic development and caused embryonic lethal. PMVK deficiency in liver tissue alleviated DEN/CCl4-induced hepatocarcinogenesis, and a small molecule inhibitor of PMVK, PMVKi5, inhibited carcinogenesis of liver and colorectal tissues [4].
In conclusion, PMVK is vital for the mevalonate pathway. Model-based research, especially through gene knockout and in vivo studies in mouse models, has revealed its significant roles in cancer-related processes such as radiotherapy response, tumor immune escape, and carcinogenesis. Understanding PMVK's functions provides potential therapeutic targets for treating diseases like lung cancer, HCC, and other cancers [1,2,4].
References:
1. Park, Seok Soon, Kwon, Mi Ri, Ju, Eun Jin, Jeong, Seong-Yun, Choi, Eun Kyung. 2023. Targeting phosphomevalonate kinase enhances radiosensitivity via ubiquitination of the replication protein A1 in lung cancer cells. In Cancer science, 114, 3583-3594. doi:10.1111/cas.15896. https://pubmed.ncbi.nlm.nih.gov/37650703/
2. Zhou, Xinyi, Chen, Zhiqiang, Yu, Yijiang, Prochownik, Edward V, Li, Youjun. 2024. Increases in 4-Acetaminobutyric Acid Generated by Phosphomevalonate Kinase Suppress CD8+ T Cell Activation and Allow Tumor Immune Escape. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2403629. doi:10.1002/advs.202403629. https://pubmed.ncbi.nlm.nih.gov/39325640/
3. Blicharz, Leszek, Czuwara, Joanna, Rudnicka, Lidia, Torrelo, Antonio. 2023. Autoinflammatory Keratinization Diseases-The Concept, Pathophysiology, and Clinical Implications. In Clinical reviews in allergy & immunology, 65, 377-402. doi:10.1007/s12016-023-08971-3. https://pubmed.ncbi.nlm.nih.gov/38103162/
4. Chen, Zhiqiang, Zhou, Xinyi, Zhou, Xiaojun, Wang, Fubing, Li, Youjun. 2023. Phosphomevalonate Kinase Controls β-Catenin Signaling via the Metabolite 5-Diphosphomevalonate. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2204909. doi:10.1002/advs.202204909. https://pubmed.ncbi.nlm.nih.gov/36808719/
5. Wang, Jiuxiang, Liu, Ying, Liu, Fei, Guo, An-Yuan, Liu, Mugen. 2016. Loss-of-function Mutation in PMVK Causes Autosomal Dominant Disseminated Superficial Porokeratosis. In Scientific reports, 6, 24226. doi:10.1038/srep24226. https://pubmed.ncbi.nlm.nih.gov/27052676/
6. Jairaman, Amit, Badiger, Vaishnavi Ashok, Raj, Spoorthy, Balan, Suma, Narayanan, Dhanya Lakshmi. 2023. A novel homozygous variant in PMVK is associated with enhanced IL1β secretion and a hyper-IgD syndrome-like phenotype. In Clinical genetics, 105, 302-307. doi:10.1111/cge.14451. https://pubmed.ncbi.nlm.nih.gov/38018277/
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