C57BL/6JCya-Gatmem1flox/Cya
Common Name:
Gatm-flox
Product ID:
S-CKO-13499
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
Price:
Contact for Pricing
Basic Information
Strain Name
Gatm-flox
Strain ID
CKOCMP-67092-Gatm-B6J-VA
Gene Name
Product ID
S-CKO-13499
Gene Alias
1810003P21Rik; AT
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
2
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Gatmem1flox/Cya mice (Catalog S-CKO-13499) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000028624
NCBI RefSeq
NM_025961
Target Region
Exon 3
Size of Effective Region
~1.0 kb
Detailed Document
Overview of Gene Research
Gatm, also known as glycine amidinotransferase or AGAT, is the rate-limiting enzyme in the creatine biosynthesis pathway. Creatine synthesis involves a series of reactions where Gatm, along with guanidinoacetate N-methyltransferase (GAMT), synthesizes creatine from arginine, glycine, and S-Adenosyl methionine [4]. Creatine metabolism is important for energy homeostasis in various tissues, and Gatm-mediated creatine synthesis occurs locally throughout the mammalian body, including in oligodendrocytes of the brain [4].
In cancer research, Gatm has been shown to play significant roles. In orthotopic mouse models, upregulation of Gatm in liver metastases promotes colorectal and breast cancer metastasis. Dietary creatine uptake or Gatm-mediated de novo synthesis enhances cancer metastasis by upregulating Snail and Slug expression via MPS1-activated Smad2 and Smad3 phosphorylation, and Gatm knockdown suppresses cancer metastasis and improves mouse survival [1]. In FLT3-ITD-mutant acute myeloid leukemia, FLT3-ITD activates the STAT5 signaling pathway, upregulating Gatm expression. Pharmacologic FLT3-ITD inhibition or genetic GATM knockdown reduces intracellular creatinine levels, leading to decreased cell proliferation and increased apoptosis in mutant cell lines, suggesting that targeting Gatm could be a therapeutic strategy [3]. In pancreatic cancer, high GATM expression is positively correlated with advanced N stage, and GATM knockdown reduces intracellular guanidinoacetic acid (GAA) levels, suppresses epithelial-mesenchymal transition (EMT), and inhibits liver metastasis [5]. In obesity-driven breast cancer, Gatm in adipocytes is required for obesity-driven tumor progression, and deletion of Gatm in adipocytes attenuates tumor growth [6].
In summary, Gatm is crucial for creatine biosynthesis, which has far-reaching implications in energy-related biological processes. Through gene-knockout (KO) and conditional-knockout (CKO) mouse models, research has revealed its important roles in cancer metastasis and tumor progression, highlighting its potential as a therapeutic target in cancer treatment. Additionally, studies on Gatm polymorphism suggest its role in statin-induced myopathy and chronic kidney disease, further expanding its significance in different disease areas [2,7].
References:
1. Zhang, Liwen, Zhu, Zijing, Yan, Huiwen, Chen, Gang, Bu, Pengcheng. 2021. Creatine promotes cancer metastasis through activation of Smad2/3. In Cell metabolism, 33, 1111-1123.e4. doi:10.1016/j.cmet.2021.03.009. https://pubmed.ncbi.nlm.nih.gov/33811821/
2. Liu, Mengyuan, Fan, Fangfang, Zhang, Yan, Li, Jianping. 2020. The association of GATM polymorphism with statin-induced myopathy: a systematic review and meta-analysis. In European journal of clinical pharmacology, 77, 349-357. doi:10.1007/s00228-020-03019-3. https://pubmed.ncbi.nlm.nih.gov/33051696/
3. Zhang, Yuan, Newsom, Kimberly J, Zhang, Mei, Kelley, Jeffry S, Starostik, Petr. 2021. GATM-Mediated Creatine Biosynthesis Enables Maintenance of FLT3-ITD-Mutant Acute Myeloid Leukemia. In Molecular cancer research : MCR, 20, 293-304. doi:10.1158/1541-7786.MCR-21-0314. https://pubmed.ncbi.nlm.nih.gov/34635505/
4. Baker, Steven Andrew, Gajera, Chandresh R, Wawro, Adam M, Corces, M Ryan, Montine, Thomas J. 2021. GATM and GAMT synthesize creatine locally throughout the mammalian body and within oligodendrocytes of the brain. In Brain research, 1770, 147627. doi:10.1016/j.brainres.2021.147627. https://pubmed.ncbi.nlm.nih.gov/34418357/
5. Yang, Jinshou, Ren, Bo, Ren, Jie, You, Lei, Zhao, Yupei. 2023. Epigenetic reprogramming-induced guanidinoacetic acid synthesis promotes pancreatic cancer metastasis and transcription-activating histone modifications. In Journal of experimental & clinical cancer research : CR, 42, 155. doi:10.1186/s13046-023-02698-x. https://pubmed.ncbi.nlm.nih.gov/37370109/
6. Maguire, Olivia A, Ackerman, Sarah E, Szwed, Sarah K, Kazak, Lawrence, Cohen, Paul. 2021. Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer. In Cell metabolism, 33, 499-512.e6. doi:10.1016/j.cmet.2021.01.018. https://pubmed.ncbi.nlm.nih.gov/33596409/
7. Liu, Bin, Gao, Xin, Teng, Haolin, Gao, Baoshan, Li, Faping. 2024. Association between GATM gene polymorphism and progression of chronic kidney disease: a mitochondrial related genome-wide Mendelian randomization study. In Scientific reports, 14, 20346. doi:10.1038/s41598-024-68448-x. https://pubmed.ncbi.nlm.nih.gov/39284843/
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