C57BL/6JCya-Gzmaem1flox/Cya
Common Name:
Gzma-flox
Product ID:
S-CKO-02806
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Gzma-flox
Strain ID
CKOCMP-14938-Gzma-B6J-VA
Gene Name
Product ID
S-CKO-02806
Gene Alias
Ctla-3; Ctla3; Hf; Hf1; SE1; TSP-1; TSP1
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
13
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Gzmaem1flox/Cya mice (Catalog S-CKO-02806) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000023897
NCBI RefSeq
NM_010370
Target Region
Exon 2
Size of Effective Region
~2.0 kb
Detailed Document
Overview of Gene Research
Granzyme A (GZMA), a serine protease, is mainly secreted by cytotoxic lymphocytes such as natural killer cells and cytotoxic T lymphocytes. It plays a crucial role in immune-mediated cell death and is involved in multiple pathways, including those related to cell apoptosis, pyroptosis, and ferroptosis [2,1]. GZMA's activity is essential for the immune system's defense against pathogens and tumor cells, and its study using genetic models like KO/CKO mouse models can reveal its role in specific biological processes and disease conditions.
In inflammatory bowel disease (IBD), GZMA secreted by CD8+CD39+ T cells suppresses GPX4-mediated ferroptosis, thereby improving intestinal mucosal barrier function. GZMA inhibits intestinal epithelial cellular PDE4B activation, triggering the cAMP/PKA/CREB cascade signaling to increase CREB nuclear translocation and initiate GPX4 transactivity. Administration of GZMA can alleviate DSS-induced colitis in vivo [1].
In chronic apical periodontitis, GZMA promotes osteoclast cell proliferation while inhibiting cell apoptosis. Inhibition of GZMA using crRNA/Cas13d leads to increased miR-25-3p expression, down-regulation of TGF-β, and subsequent decrease in PAR1 expression within the PARs pathway [3].
In hepatocellular carcinoma, the interaction between GZMA secreted by cytotoxic cells and F2R expressed by tumor cells activates the JAK2/STAT1 signaling pathway, inducing tumor suppression and T cell-mediated killing of tumor cells. Low expression of GZMA and F2R in tumor tissues is correlated with aggressive clinicopathological characteristics and poor prognosis [4].
In conclusion, GZMA is a key molecule in the immune response and is involved in diverse biological processes. Through model-based research, its functions in diseases such as IBD, chronic apical periodontitis, and hepatocellular carcinoma have been revealed. These findings suggest that GZMA could potentially be a therapeutic target for these diseases, highlighting the importance of further research on GZMA's role and mechanism in various pathological conditions.
References：
1. Niu, Rongwei, Lan, Jiaoli, Liang, Danxia, Gong, Sitang, Yang, Min. 2024. GZMA suppressed GPX4-mediated ferroptosis to improve intestinal mucosal barrier function in inflammatory bowel disease. In Cell communication and signaling : CCS, 22, 474. doi:10.1186/s12964-024-01836-y. https://pubmed.ncbi.nlm.nih.gov/39367435/
2. Zhou, Zhiwei, He, Huabin, Wang, Kun, Ding, Jingjin, Shao, Feng. 2020. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. In Science (New York, N.Y.), 368, . doi:10.1126/science.aaz7548. https://pubmed.ncbi.nlm.nih.gov/32299851/
3. Jia, Tingting, Yuan, Fang, Tao, Jingqiao, Zhang, Bin, Li, Hongbo. 2023. CRISPR/Cas13d targeting GZMA in PARs pathway regulates the function of osteoclasts in chronic apical periodontitis. In Cellular & molecular biology letters, 28, 70. doi:10.1186/s11658-023-00477-2. https://pubmed.ncbi.nlm.nih.gov/37626297/
4. Gao, Yuxue, Xu, Qingguo, Li, Xinqiang, Chen, Dexi, Yang, Tongwang. 2022. Heterogeneity induced GZMA-F2R communication inefficient impairs antitumor immunotherapy of PD-1 mAb through JAK2/STAT1 signal suppression in hepatocellular carcinoma. In Cell death & disease, 13, 213. doi:10.1038/s41419-022-04654-7. https://pubmed.ncbi.nlm.nih.gov/35256589/
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