C57BL/6JCya-Mettl8em1/Cya
Common Name:
Mettl8-KO
Product ID:
S-KO-16539
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Mettl8-KO
Strain ID
KOCMP-228019-Mettl8-B6J-VB
Gene Name
Product ID
S-KO-16539
Gene Alias
Tip
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
2
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Mettl8em1/Cya mice (Catalog S-KO-16539) 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, or methyltransferase-like 8, is a gene encoding an enzyme involved in RNA modification. It is a key factor in the 3-methylcytosine (m3C) modification of mitochondrial tRNAs, which is crucial for mitochondrial protein translation, respiration, and overall cellular energy metabolism. The role of Mettl8 in biological systems can be studied using genetic models such as knockout mice [1,2,3].
In mouse embryonic cortical neural stem cells, Mettl8 is localized in mitochondria and installs m3C specifically on mitochondrial tRNAThr/Ser(UCN). Deletion of Mettl8 in these cells leads to reduced mitochondrial protein translation, attenuated respiration activity, and impaired embryonic cortical neural stem cell maintenance in vivo, which 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, METTL8 levels are high, correlating with lower patient survival and enhanced respiratory chain activity. METTL8 knockout cells show a reduction in respiratory chain activity, while overexpression increases it. Mitochondrial ribosome profiling in knockout cells uncovered mitoribosome stalling on mt-tRNASer(UCN)-and mt-tRNAThr-dependent codons, and reduced incorporation of mitochondrially encoded proteins ND6 and ND1 into complex I [2]. In glioblastoma stem cells (GSCs), METTL8 is localized to the mitochondrial matrix, where it installs m3C on mt-tRNAThr/Ser(UCN) for mitochondrial translation and respiration. High METTL8 expression in glioblastoma is attributed to histone variant H2AZ-mediated chromatin accessibility of HIF1α and portends inferior patient outcome. Depletion of METTL8 impairs GSC self-renewal and differentiation, retarding tumor growth in an intracranial GBM xenograft model, and also inactivates the RTK/Akt axis, leading to heightened sensitivity to Akt inhibitor treatment [3].
In conclusion, Mettl8 is essential for the m3C modification of mitochondrial tRNAs, which is crucial for mitochondrial translation, respiration, and cell fate maintenance in processes like cortical neurogenesis. Its dysregulation is associated with diseases such as pancreatic cancer and glioblastoma. The use of Mettl8 knockout or conditional knockout mouse models has provided valuable insights into its role in these biological processes and disease conditions, helping to understand the underlying mechanisms and potentially paving the way for new therapeutic strategies.
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/
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