C57BL/6NCya-Alkbh1em1/Cya
Common Name:
Alkbh1-KO
Product ID:
S-KO-04770
Background:
C57BL/6NCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Alkbh1-KO
Strain ID
KOCMP-211064-Alkbh1-B6N-VA
Gene Name
Product ID
S-KO-04770
Gene Alias
2700073G19Rik; Abh; Alkbh; alkB; hABH
Background
C57BL/6NCya
NCBI ID
Modification
Conventional knockout
Chromosome
12
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6NCya-Alkbh1em1/Cya mice (Catalog S-KO-04770) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000162961
NCBI RefSeq
NM_001102565
Target Region
Exon 2~3
Size of Effective Region
~2.0 kb
Detailed Document
Overview of Gene Research
Alkbh1, or AlkB homolog 1, is a member of the AlkB superfamily of Fe (II) and α-ketoglutarate-dependent dioxygenases. It functions as a demethylase, reversing DNA methylation and repairing DNA damage. It is involved in multiple biological processes such as translation regulation, through mediating tRNA demethylation [2]. It also plays roles in various pathways like HIF-1α-mediated glycolysis and is associated with numerous diseases, including cancer, vascular calcification, and neurological and genetic related disorders [3]. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.
In the context of vascular calcification in chronic kidney disease, decreased DNA N6-methyladenine (6mA) demethylation due to upregulation of ALKBH1 was observed. ALKBH1 overexpression aggravated while its depletion blunted vascular calcification progression and osteogenic reprogramming in vivo and in vitro. Mechanistically, ALKBH1-demethylated DNA 6mA modification facilitated the binding of Oct4 to BMP2 promoter, activating BMP2 transcription, which led to osteogenic reprogramming of vascular smooth muscle cells and subsequent vascular calcification progression [1]. In gastric cancer, ALKBH1 knockout in mice impaired chemically induced gastric carcinogenesis. ALKBH1 mediated DNA 6mA demethylation to repress gene expression, specifically inhibiting NRF1-driven transcription of downstream targets in the AMP-activated protein kinase (AMPK) signaling pathway, thus promoting tumorigenesis [4]. In adipogenic differentiation, knockdown of ALKBH1 in human mesenchymal stem cells and 3T3-L1 preadipocytes inhibited adipogenesis, while overexpression increased it. RNA-seq and N6-mA-DNA-IP-seq analyses identified HIF-1 signaling as a crucial downstream target of ALKBH1 activity [5].
In conclusion, Alkbh1 is a significant demethylase involved in multiple biological functions. Through model-based research, especially KO mouse models, its role in diseases like vascular calcification, gastric cancer, and adipogenic differentiation has been revealed. These findings contribute to understanding the underlying mechanisms of these diseases and potentially developing new therapeutic strategies targeting Alkbh1.
References:
1. Ouyang, Liu, Su, Xiaoyan, Li, Wenxin, Chen, Jie, Huang, Hui. . ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease. In The Journal of clinical investigation, 131, . doi:10.1172/JCI146985. https://pubmed.ncbi.nlm.nih.gov/34003800/
2. Liu, Fange, Clark, Wesley, Luo, Guanzheng, Pan, Tao, He, Chuan. 2016. ALKBH1-Mediated tRNA Demethylation Regulates Translation. In Cell, 167, 816-828.e16. doi:10.1016/j.cell.2016.09.038. https://pubmed.ncbi.nlm.nih.gov/27745969/
3. Zhang, Ying, Wang, Caiyan. 2021. Demethyltransferase AlkBH1 substrate diversity and relationship to human diseases. In Molecular biology reports, 48, 4747-4756. doi:10.1007/s11033-021-06421-x. https://pubmed.ncbi.nlm.nih.gov/34046849/
4. Wang, Xiaohong, Wong, Chi Chun, Chen, Huarong, Ji, Jiafu, Yu, Jun. 2023. The N6-methyladenine DNA demethylase ALKBH1 promotes gastric carcinogenesis by disrupting NRF1 binding capacity. In Cell reports, 42, 112279. doi:10.1016/j.celrep.2023.112279. https://pubmed.ncbi.nlm.nih.gov/36989111/
5. Liu, Yuting, Chen, Yaqian, Wang, Yuan, Liu, Weiqing, Yuan, Quan. 2021. DNA demethylase ALKBH1 promotes adipogenic differentiation via regulation of HIF-1 signaling. In The Journal of biological chemistry, 298, 101499. doi:10.1016/j.jbc.2021.101499. https://pubmed.ncbi.nlm.nih.gov/34922943/
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