C57BL/6JCya-Hk1em1flox/Cya
Common Name:
Hk1-flox
Product ID:
S-CKO-02895
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Hk1-flox
Strain ID
CKOCMP-15275-Hk1-B6J-VA
Gene Name
Product ID
S-CKO-02895
Gene Alias
Hk-1; Hk1-s; dea; mHk1-s
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
10
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Hk1em1flox/Cya mice (Catalog S-CKO-02895) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000099691
NCBI RefSeq
NM_001146100
Target Region
Exon 2
Size of Effective Region
~1.6 kb
Detailed Document
Overview of Gene Research
HK1, short for hexokinase 1, is a key enzyme that catalyzes the first step of glycolysis, phosphorylating glucose to glucose-6-phosphate. This reaction is crucial as the product, glucose-6-phosphate, can be directed into different metabolic routes such as glycolysis or the pentose phosphate pathway. HK1 is involved in various biological processes, including energy metabolism, and is associated with numerous diseases [2].
In hepatic fibrosis, TGF-β stimulates the palmitoylation of HK1 in hepatic stellate cells (HSCs), facilitating its secretion via large extracellular vesicles. These vesicles are then taken up by hepatocellular carcinoma (HCC) cells, accelerating glycolysis and HCC progression. In HSCs, Nur77 transcriptionally activates ABHD17B to inhibit HK1 palmitoylation, but TGF-β-activated Akt represses Nur77, promoting HK1 release. The small molecule PDNPA can bind Nur77, blocking Akt-mediated Nur77 degradation and inhibiting HK1 release, thus potentially inhibiting HCC progression [1].
Mice lacking the HK1 mitochondrial binding domain (ΔE1HK1) showed a hyper-inflammatory response, decreased glucose flux below GAPDH, and increased upstream flux through the PPP due to cytosolic HK1 binding with S100A8/A9, leading to GAPDH nitrosylation [2].
In D-galactose-induced aging mice, alpinetin alleviated cognitive dysfunction and neuronal damage by inhibiting the Drp1/HK1/NLRP3 pathway-suppressed mitochondrial inflammation, up-regulating HK1 expression [3].
Non-coding variants in HK1 can disrupt its tissue-specific silencing in pancreatic beta cells, causing congenital hyperinsulinism [4].
In breast cancer, ErbB2 upregulates HK1, and siHK1 significantly inhibits the proliferation, migration, and invasion of ErbB2-overexpressing breast cancer cells [5].
Monoallelic HK1 variants in individuals cause a neurodevelopmental disorder (NDD), with a biomarker profile of low CSF glucose, low CSF/blood glucose, and high CSF lactate [6].
During energy stress, HK1 forms rings around mitochondria, preventing mitochondrial fission by displacing Drp1 from Mff and Fis1, and affecting mitochondrial metabolic activity [7].
miR-34a can target HK1, and HK1 replenishment reverses mesenchymal stem cell (MSC) senescence and reinforces glycolysis [8].
A de novo HK1 variant was found in an individual with a clinical diagnosis consistent with Boucher-Neuhäuser syndrome, expanding the known HK1 genotypic and phenotypic spectrum [9].
In conclusion, HK1 is essential for glycolysis and plays a significant role in multiple diseases including HCC, congenital hyperinsulinism, breast cancer, NDD, and aging-associated cognitive impairment. Studies using gene-modified mouse models, like ΔE1HK1 mice, have revealed its role in regulating glucose metabolism and inflammatory responses. Understanding HK1's function provides insights into disease mechanisms and potential therapeutic targets.
References:
1. Chen, Qi-Tao, Zhang, Zhi-Yuan, Huang, Qiao-Ling, Deng, Xianming, Wu, Qiao. 2022. HK1 from hepatic stellate cell-derived extracellular vesicles promotes progression of hepatocellular carcinoma. In Nature metabolism, 4, 1306-1321. doi:10.1038/s42255-022-00642-5. https://pubmed.ncbi.nlm.nih.gov/36192599/
2. De Jesus, Adam, Keyhani-Nejad, Farnaz, Pusec, Carolina M, Weinberg, Samuel E, Ardehali, Hossein. 2022. Hexokinase 1 cellular localization regulates the metabolic fate of glucose. In Molecular cell, 82, 1261-1277.e9. doi:10.1016/j.molcel.2022.02.028. https://pubmed.ncbi.nlm.nih.gov/35305311/
3. Chen, Yuanyuan, Yang, Chuan, Zou, Mi, Liu, Xiao, Xu, Shijun. 2023. Inhibiting mitochondrial inflammation through Drp1/HK1/NLRP3 pathway: A mechanism of alpinetin attenuated aging-associated cognitive impairment. In Phytotherapy research : PTR, 37, 2454-2471. doi:10.1002/ptr.7767. https://pubmed.ncbi.nlm.nih.gov/36772986/
4. Wakeling, Matthew N, Owens, Nick D L, Hopkinson, Jessica R, Richardson, Sarah J, Flanagan, Sarah E. 2022. Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism. In Nature genetics, 54, 1615-1620. doi:10.1038/s41588-022-01204-x. https://pubmed.ncbi.nlm.nih.gov/36333503/
5. Ma, Xuejiao, Chen, Jingruo, Huang, Bohan, Yu, Rong, Zhao, Yuhua. 2023. ErbB2-upregulated HK1 and HK2 promote breast cancer cell proliferation, migration and invasion. In Medical oncology (Northwood, London, England), 40, 154. doi:10.1007/s12032-023-02008-7. https://pubmed.ncbi.nlm.nih.gov/37079118/
6. Wortmann, Saskia B, Feichtinger, Rene G, Abela, Lucia, Boltshauser, Eugen, Willemsen, Michel A. 2024. Clinical, Neuroimaging, and Metabolic Footprint of the Neurodevelopmental Disorder Caused by Monoallelic HK1 Variants. In Neurology. Genetics, 10, e200146. doi:10.1212/NXG.0000000000200146. https://pubmed.ncbi.nlm.nih.gov/38617198/
7. Pilic, Johannes, Gottschalk, Benjamin, Bourgeois, Benjamin, Graier, Wolfgang F, Malli, Roland. 2024. Hexokinase 1 forms rings that regulate mitochondrial fission during energy stress. In Molecular cell, 84, 2732-2746.e5. doi:10.1016/j.molcel.2024.06.009. https://pubmed.ncbi.nlm.nih.gov/38981483/
8. Sun, Yanan, Zhang, Chang, Ma, Qianhui, Li, Yan, He, Xu. 2024. MiR-34a-HK1 signal axis retards bone marrow mesenchymal stem cell senescence via ameliorating glycolytic metabolism. In Stem cell research & therapy, 15, 238. doi:10.1186/s13287-024-03857-3. https://pubmed.ncbi.nlm.nih.gov/39080798/
9. Peretz, Ryan H, Zein, Wadih M, Hufnagel, Robert B, Gahl, William, Toro, Camilo. 2022. A de novo hexokinase 1 (HK1) variant presenting as Boucher-Neuhäuser syndrome. In American journal of medical genetics. Part A, 191, 624-629. doi:10.1002/ajmg.a.63045. https://pubmed.ncbi.nlm.nih.gov/36541585/
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