C57BL/6JCya-Gclmem1/Cya
Common Name:
Gclm-KO
Product ID:
S-KO-02250
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Gclm-KO
Strain ID
KOCMP-14630-Gclm-B6J-VA
Gene Name
Product ID
S-KO-02250
Gene Alias
Gcmc; Glclr
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
3
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Gclmem1/Cya mice (Catalog S-KO-02250) 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, the glutamate-cysteine ligase modifier subunit, is a key component of the rate-limiting enzyme glutamate cysteine ligase (GCL) in glutathione (GSH) biosynthesis [1,2]. GSH is a crucial antioxidant in mammalian tissues, involved in defending against oxidative stress, redox signaling, xenobiotic detoxification, and regulating processes like cell proliferation, apoptosis, immune function, and fibrogenesis [1,2]. The Gclm-containing GCL complex is regulated at multiple levels, often in coordination with GSH synthase, and is influenced by transcription factors such as Nrf2, AP-1, and NFκB [1,2]. Genetic models, like gene knockout mice, are valuable for studying Gclm's function.
In Gclm null mice, which have severely reduced GSH levels (expressing about 10% of normal GSH), there is an up-regulation of redox-regulated genes. Surprisingly, these mice are less susceptible to certain types of oxidative damage, display a lean phenotype, resistance to high-fat diet-induced diabetes and obesity, improved insulin and glucose tolerance, and decreased lipogenesis-related gene expression, and this phenotype persists into old age and under cadmium exposure [6]. In colorectal cancer, loss of Gclm increases sensitivity to platinum-based chemotherapy, as nuclear-translocated Gclm promotes chemoresistance through competitively interacting with NF-κB-repressing factor to enhance NF-κB activity [3]. In addition, in diseases like non-alcoholic fatty liver disease, spermidine mitigates ferroptosis in AML-12 cells by upregulating Gclm expression through the ATF4 pathway [4]. In acute kidney injury to chronic kidney disease transition, REST transcriptionally represses Gclm expression, and its knockdown alleviates injury by attenuating ferroptosis [5].
In conclusion, Gclm is essential for GSH synthesis and redox regulation. Studies using Gclm KO mouse models have revealed its roles in various disease conditions, including diabetes-related phenotypes, chemoresistance in colorectal cancer, non-alcoholic fatty liver disease, and the transition from acute to chronic kidney disease. Understanding Gclm's function provides insights into disease mechanisms and potential therapeutic targets.
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/
6. Schaupp, Christopher M, Botta, Dianne, White, Collin C, MacDonald, James, Kavanagh, Terrance J. 2021. Persistence of improved glucose homeostasis in Gclm null mice with age and cadmium treatment. In Redox biology, 49, 102213. doi:10.1016/j.redox.2021.102213. https://pubmed.ncbi.nlm.nih.gov/34953454/
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