C57BL/6JCya-Dimt1em1/Cya
Common Name:
Dimt1-KO
Product ID:
S-KO-18494
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Dimt1-KO
Strain ID
KOCMP-66254-Dimt1-B6J-VB
Gene Name
Product ID
S-KO-18494
Gene Alias
1500031M22Rik; Dimt1l
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
13
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Dimt1em1/Cya mice (Catalog S-KO-18494) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000022203
NCBI RefSeq
NM_025447
Target Region
Exon 3~6
Size of Effective Region
~2.5 kb
Detailed Document
Overview of Gene Research
Dimt1, short for dimethyladenosine transferase 1, is an evolutionarily conserved RNA N6,6-dimethyladenosine (m26,6A) methyltransferase. It plays a crucial role in ribosome biogenesis, and its catalytic activity is indispensable for cell viability and protein synthesis. Dimt1 is involved in pathways related to inter-generational hormesis, ribosomal processing, and may impact mitochondrial function. Genetic models such as Caenorhabditis elegans are valuable for studying its functions [1,2].
In C. elegans, parental starvation leads to inter-generational hormesis in progeny, which is accompanied by an increase in N6'-dimethyl adenosine (m6,2A) on 18S ribosomal RNA. DIMT-1/DIMT1 was identified as the m6,2A methyltransferase required for this inter-generational hormesis [1]. In human cells, DIMT1 generates m26,6A not only in 18S rRNA but also in small RNAs, and cells expressing catalytically inactive DIMT1 variants show decreased protein synthesis and cell viability [2]. In acute myeloid leukemia (AML), DIMT1 is essential for proliferation through a non-catalytic function. Targeting a positively charged cleft of DIMT1, remote from the catalytic site, weakens its binding to rRNA and mislocalizes it, affecting AML cell proliferation [3]. In gastric carcinoma, high DIMT1 expression correlates with tumor progression and poor prognosis [4]. In insects and C. elegans, the putative ortholog of human DIMT1 regulates lifespan [5]. In β-cells, DIMT1 controls protein synthesis, mitochondrial function, and insulin secretion, and its deficiency leads to perturbed insulin secretion, a potential pathogenic process in type 2 diabetes (T2D) [6]. In thyroid cancer, a PARP inhibitor inhibits DIMT1 transcription, leading to global translation inhibition [7]. Structural studies in human cells show that the catalytic activity of DIMT1 is involved in protein translation, and its overall protein scaffold is essential for 40S assembly [8]. Structural and functional characterization of archaeal DIMT1 reveals unique protein dynamics for efficient catalysis [9]. A study on the positively charged cleft of DIMT1 identified the minimum region to target for cell proliferation regulation [10].
In conclusion, Dimt1 is essential for ribosome biogenesis, cell viability, and protein synthesis. Model-based research, including studies in C. elegans, insects, and human cell lines, has revealed its roles in various biological processes and diseases such as inter-generational hormesis, cancer (AML, gastric carcinoma, thyroid cancer), lifespan regulation, and T2D. These findings contribute to understanding the molecular mechanisms underlying these biological phenomena and diseases, potentially guiding the development of new therapeutic strategies.
References:
1. Liberman, Noa, Rothi, M Hafiz, Gerashchenko, Maxim V, Gladyshev, Vadim N, Greer, Eric Lieberman. 2023. 18S rRNA methyltransferases DIMT1 and BUD23 drive intergenerational hormesis. In Molecular cell, 83, 3268-3282.e7. doi:10.1016/j.molcel.2023.08.014. https://pubmed.ncbi.nlm.nih.gov/37689068/
2. Shen, Hui, Gonskikh, Yulia, Stoute, Julian, Liu, Kathy Fange. 2021. Human DIMT1 generates N26,6A-dimethylation-containing small RNAs. In The Journal of biological chemistry, 297, 101146. doi:10.1016/j.jbc.2021.101146. https://pubmed.ncbi.nlm.nih.gov/34473991/
3. Gonskikh, Yulia, Stoute, Julian, Shen, Hui, Shi, Junwei, Liu, Kathy Fange. 2023. Noncatalytic regulation of 18S rRNA methyltransferase DIMT1 in acute myeloid leukemia. In Genes & development, 37, 321-335. doi:10.1101/gad.350298.122. https://pubmed.ncbi.nlm.nih.gov/37024283/
4. Liu, Guangyi, Peng, Xudong, Cai, Yongqian, Zha, Lang, Wang, Ziwei. 2017. DIMT1 overexpression correlates with progression and prognosis in gastric carcinoma. In Human pathology, 70, 35-42. doi:10.1016/j.humpath.2017.02.034. https://pubmed.ncbi.nlm.nih.gov/28601661/
5. Tao, Mei, Chen, Jiani, Cui, Chunlai, Huang, Jianhua, Shen, Xing-Xing. 2024. Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes. In Nature aging, 4, 1076-1088. doi:10.1038/s43587-024-00641-z. https://pubmed.ncbi.nlm.nih.gov/38834883/
6. Verma, Gaurav, Bowen, Alexander, Gheibi, Sevda, Fex, Malin, Mulder, Hindrik. 2022. Ribosomal biogenesis regulator DIMT1 controls β-cell protein synthesis, mitochondrial function, and insulin secretion. In The Journal of biological chemistry, 298, 101692. doi:10.1016/j.jbc.2022.101692. https://pubmed.ncbi.nlm.nih.gov/35148993/
7. Hou, Xiukun, Tian, Mengran, Ning, Junya, Gao, Ming, Zheng, Xiangqian. 2023. PARP inhibitor shuts down the global translation of thyroid cancer through promoting Pol II binding to DIMT1 pause. In International journal of biological sciences, 19, 3970-3986. doi:10.7150/ijbs.81895. https://pubmed.ncbi.nlm.nih.gov/37564214/
8. Shen, Hui, Stoute, Julian, Liu, Kathy Fange. 2020. Structural and catalytic roles of the human 18S rRNA methyltransferases DIMT1 in ribosome assembly and translation. In The Journal of biological chemistry, 295, 12058-12070. doi:10.1074/jbc.RA120.014236. https://pubmed.ncbi.nlm.nih.gov/32616653/
9. Saha, Sayan, Kanaujia, Shankar Prasad. 2024. Structural and functional characterization of archaeal DIMT1 unveils distinct protein dynamics essential for efficient catalysis. In Structure (London, England : 1993), 32, 1760-1775.e7. doi:10.1016/j.str.2024.07.013. https://pubmed.ncbi.nlm.nih.gov/39146930/
10. Wei, Xiaoyu, Sampson, Nora, Figueroa Mendoza, Sarai Maria, Gonskikh, Yulia, Liu, Kathy Fange. 2025. Fault-Tolerance Study on a Positive-Charged Cleft in 18S rRNA Methyltransferase DIMT1. In Biochemistry, 64, 525-532. doi:10.1021/acs.biochem.4c00319. https://pubmed.ncbi.nlm.nih.gov/39762086/
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