C57BL/6JCya-Mettl8em1flox/Cya
Common Name:
Mettl8-flox
Product ID:
S-CKO-07149
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Mettl8-flox
Strain ID
CKOCMP-228019-Mettl8-B6J-VA
Gene Name
Product ID
S-CKO-07149
Gene Alias
Tip
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
2
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Mettl8em1flox/Cya mice (Catalog S-CKO-07149) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000112186
NCBI RefSeq
NM_145524
Target Region
Exon 3
Size of Effective Region
~1.4 kb
Detailed Document
Overview of Gene Research
Mettl8, also known as Methyltransferase-like 8, is an RNA methyltransferase. It is crucial for installing 3-methylcytosine (m3C) modification on mitochondrial tRNAs, especially mt-tRNAThr/Ser(UCN), which is involved in mitochondrial translation and respiration processes, and thus holds significance in various biological systems [1,2,3,4,5,6].
In mouse embryonic cortical neural stem cells, conditional Mettl8 deletion leads to reduced mitochondrial protein translation, attenuated respiration activity, and impaired embryonic cortical neural stem cell maintenance in vivo. These defects can be rescued by enhancing mitochondrial functions. Similarly, in human forebrain cortical organoids, METTL8 promotes mitochondrial protein expression and neural stem cell maintenance [1]. In pancreatic cancer, high METTL8 levels correlate with lower patient survival and enhanced respiratory chain activity. METTL8 knockout cells show reduced respiratory chain activity, and mitochondrial ribosome profiling reveals mitoribosome stalling on mt-tRNASer(UCN)-and mt-tRNAThr-dependent codons, along with reduced incorporation of ND6 and ND1 into complex I [2]. In glioblastoma (GBM), METTL8 depletion in glioma stem cells (GSCs) impairs self-renewal and differentiation, retarding tumor growth in an intracranial GBM xenograft model. It also decreases HIF1α protein levels, inactivating the RTK/Akt axis and increasing sensitivity to Akt inhibitor treatment [3].
In conclusion, Mettl8-mediated m3C modification of mitochondrial tRNAs is essential for optimal mitochondrial translation and respiration. The use of Mettl8 KO/CKO mouse models has revealed its role in embryonic cortical neurogenesis, and its dysregulation in diseases like pancreatic cancer and GBM, providing potential therapeutic targets for these diseases.
References:
1. Zhang, Feng, Yoon, Kijun, Zhang, Daniel Y, Ming, Guo-Li, Song, Hongjun. 2023. Epitranscriptomic regulation of cortical neurogenesis via Mettl8-dependent mitochondrial tRNA m3C modification. In Cell stem cell, 30, 300-311.e11. doi:10.1016/j.stem.2023.01.007. https://pubmed.ncbi.nlm.nih.gov/36764294/
2. Schöller, Eva, Marks, James, Marchand, Virginie, Hafner, Markus, Meister, Gunter. 2021. Balancing of mitochondrial translation through METTL8-mediated m3C modification of mitochondrial tRNAs. In Molecular cell, 81, 4810-4825.e12. doi:10.1016/j.molcel.2021.10.018. https://pubmed.ncbi.nlm.nih.gov/34774131/
3. Lee, Bernice Woon Li, Chuah, You Heng, Yoon, Jeehyun, Lin, Zhewang, Ong, Derrick Sek Tong. 2024. METTL8 links mt-tRNA m3C modification to the HIF1α/RTK/Akt axis to sustain GBM stemness and tumorigenicity. In Cell death & disease, 15, 338. doi:10.1038/s41419-024-06718-2. https://pubmed.ncbi.nlm.nih.gov/38744809/
4. Lentini, Jenna M, Bargabos, Rachel, Chen, Chen, Fu, Dragony. 2022. Methyltransferase METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs. In The Journal of biological chemistry, 298, 101788. doi:10.1016/j.jbc.2022.101788. https://pubmed.ncbi.nlm.nih.gov/35247384/
5. Huang, Meng-Han, Wang, Jin-Tao, Zhang, Jian-Hui, Wang, En-Duo, Zhou, Xiao-Long. 2023. Mitochondrial RNA m3C methyltransferase METTL8 relies on an isoform-specific N-terminal extension and modifies multiple heterogenous tRNAs. In Science bulletin, 68, 2094-2105. doi:10.1016/j.scib.2023.08.002. https://pubmed.ncbi.nlm.nih.gov/37573249/
6. Kleiber, Nicole, Lemus-Diaz, Nicolas, Stiller, Carina, Bohnsack, Katherine E, Bohnsack, Markus T. 2022. The RNA methyltransferase METTL8 installs m3C32 in mitochondrial tRNAsThr/Ser(UCN) to optimise tRNA structure and mitochondrial translation. In Nature communications, 13, 209. doi:10.1038/s41467-021-27905-1. https://pubmed.ncbi.nlm.nih.gov/35017528/
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