C57BL/6JCya-Gclmem1flox/Cya
Common Name:
Gclm-flox
Product ID:
S-CKO-02650
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Gclm-flox
Strain ID
CKOCMP-14630-Gclm-B6J-VA
Gene Name
Product ID
S-CKO-02650
Gene Alias
Gcmc; Glclr
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
3
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Gclmem1flox/Cya mice (Catalog S-CKO-02650) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000029769
NCBI RefSeq
NM_008129
Target Region
Exon 4~5
Size of Effective Region
~2.2 kb
Detailed Document
Overview of Gene Research
Gclm, also known as glutamate-cysteine ligase modifier subunit, is a crucial component of the rate-limiting enzyme glutamate cysteine ligase (GCL) in glutathione (GSH) biosynthesis. GSH is a key intracellular antioxidant involved in detoxification, antioxidant defense, and modulation of cell proliferation. GCL, composed of Gclm and a catalytic subunit Gclc, is tightly regulated and plays a vital role in maintaining redox homeostasis [1,2].
In colorectal cancer, knockout of Gclm using a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen increased the sensitivity of cells to platinum-based chemotherapy. Mechanistically, nuclear Gclm was found to competitively interact with NF-κB-repressing factor (NKRF) to promote NF-κB activity and chemoresistance. Phosphorylation of Gclm by P38 MAPK at T17 led to its nuclear translocation in response to platinum drug treatment [3].
In addition, in the context of non-alcoholic fatty liver disease (NAFLD), knockdown of activating transcription factor 4 (ATF4) reversed the upregulation of Gclm by spermidine, which otherwise mitigated ferroptosis in free fatty acid-induced AML-12 cells through the ATF4/SLC7A11/Gclm/GPX4 pathway [4].
Also, in the transition from acute kidney injury (AKI) to chronic kidney disease (CKD), renal tubule-specific knockout of Rest alleviated AKI and its progression to CKD. REST was found to transcriptionally repress Gclm expression via directly binding to its promoter region, and suppression of ferroptosis was responsible for REST-knockdown-induced amelioration of hypoxia-reoxygenation injury [5].
In conclusion, Gclm is essential for GSH synthesis and redox regulation. Model-based research, especially gene knockout studies in mice, has revealed its role in diseases such as colorectal cancer, NAFLD, and the AKI-to-CKD transition. These findings highlight the significance of Gclm in understanding disease mechanisms and potentially developing targeted therapies.
References:
1. Lu, Shelly C. 2012. Glutathione synthesis. In Biochimica et biophysica acta, 1830, 3143-53. doi:10.1016/j.bbagen.2012.09.008. https://pubmed.ncbi.nlm.nih.gov/22995213/
2. Lu, Shelly C. 2008. Regulation of glutathione synthesis. In Molecular aspects of medicine, 30, 42-59. doi:10.1016/j.mam.2008.05.005. https://pubmed.ncbi.nlm.nih.gov/18601945/
3. Lin, Jin-Fei, Liu, Ze-Xian, Chen, Dong-Liang, Ju, Huai-Qiang, Xu, Rui-Hua. 2025. Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function. In Nature communications, 16, 263. doi:10.1038/s41467-024-55568-1. https://pubmed.ncbi.nlm.nih.gov/39747101/
4. Zhang, Jia, Zhang, Tao, Chen, Yihang, Zhao, Yuqian, Lu, Gaofeng. 2024. Spermidine mitigates ferroptosis in free fatty acid-induced AML-12 cells through the ATF4/SLC7A11/GCLM/GPX4 pathway. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1869, 159560. doi:10.1016/j.bbalip.2024.159560. https://pubmed.ncbi.nlm.nih.gov/39181440/
5. Gong, Shuiqin, Zhang, Aihong, Yao, Mengying, Huang, Yinghui, Zhao, Jinghong. 2023. REST contributes to AKI-to-CKD transition through inducing ferroptosis in renal tubular epithelial cells. In JCI insight, 8, . doi:10.1172/jci.insight.166001. https://pubmed.ncbi.nlm.nih.gov/37288660/
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