Sat1-flox 基因敲除小鼠

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产品名称

Sat1-flox 基因敲除小鼠

产品编号

S-CKO-04918

品系全称

C57BL/6JCya-Sat1em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-20229-Sat1-B6J-VA

品系状态

使用本品系发表的文献需注明: Sat1-flox 基因敲除小鼠 mice (Strain S-CKO-04918) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
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小计:
询价
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
spermidine/spermine N1-acetyl transferase 1
基因别称
SSAT,Sat
染色体号
Chr X (Mouse)
转录本 ID
NCBI: NM_009121 | Ensembl: ENSMUST00000026318
修饰方式
条件性基因敲除
靶向范围
Exon 1~6
敲除长度
~4.9 kb
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
MGI:98233Mice homozygous for a knock-out allele exhibit reduced female fertility, increased percent body fat and total fat pad weight, abnormal liver and white adipose tissue physiology, abnormal aerobic energy metabolism, increased serum leptin levels, and increased weight gain on a high-fat diet.
SAT1,全称为spermidine/spermine N1-acetyltransferase 1,是一种在多胺代谢中发挥关键作用的酶。它主要负责催化精脒和精胺的N1-乙酰化反应,将它们转化为腐胺。这一过程是多胺分解代谢的限速步骤,对于维持细胞内多胺水平的动态平衡至关重要。多胺是一类在细胞生长、分化、增殖和凋亡中发挥重要作用的低分子量含氮有机化合物。它们在DNA合成、细胞分裂和细胞信号传导等生物学过程中扮演着重要角色。

在肿瘤抑制方面,SAT1的表达与p53蛋白的活性密切相关。p53是一种肿瘤抑制因子,通过调控细胞周期、细胞衰老和细胞凋亡等过程来抑制肿瘤的发生和发展。研究表明,SAT1是p53的转录靶点之一。在细胞中,p53可以激活SAT1的表达,从而促进精脒和精胺的乙酰化,进而降低细胞内多胺水平。低多胺水平可以增加细胞对氧化应激的敏感性,从而诱导细胞发生铁死亡,这是一种由脂质过氧化引起的细胞死亡方式。铁死亡的诱导可以抑制肿瘤的生长和扩散,从而发挥肿瘤抑制的作用。

除了在肿瘤抑制中的作用,SAT1还与多种疾病的发生和发展相关。例如,在神经性疼痛中,SAT1的表达水平升高,并通过与ALOX15信号通路的相互作用,抑制铁死亡的发生,从而缓解神经性疼痛的症状。在急性胰腺炎中,SAT1的表达水平升高,并且与巨噬细胞的浸润和多种信号通路的异常调节相关,提示SAT1可能参与急性胰腺炎的免疫微环境调节。

此外,SAT1的表达还与阿尔茨海默病的发生和发展相关。研究表明,在阿尔茨海默病患者的大脑中,SAT1的表达水平降低,并且与铁死亡的发生相关。SAT1的表达水平降低可能导致细胞内多胺水平升高,进而抑制cGAS的活性,影响DNA传感器的功能,从而影响免疫反应的发生。

综上所述,SAT1是一种在多胺代谢中发挥关键作用的酶,参与调控细胞内多胺水平的动态平衡。SAT1的表达与p53蛋白的活性密切相关,通过促进铁死亡的诱导来抑制肿瘤的发生和发展。此外,SAT1还与多种疾病的发生和发展相关,包括神经性疼痛、急性胰腺炎和阿尔茨海默病等。对SAT1的研究有助于深入理解多胺代谢的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8,9,10]。

参考文献:
1. Ou, Yang, Wang, Shang-Jui, Li, Dawei, Chu, Bo, Gu, Wei. 2016. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses. In Proceedings of the National Academy of Sciences of the United States of America, 113, E6806-E6812. doi:. https://pubmed.ncbi.nlm.nih.gov/27698118/
2. Murthy, Divya, Attri, Kuldeep S, Shukla, Surendra K, Wellen, Kathryn E, Singh, Pankaj K. 2024. Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2-SP1-SAT1 axis. In Nature cell biology, 26, 613-627. doi:10.1038/s41556-024-01372-4. https://pubmed.ncbi.nlm.nih.gov/38429478/
3. Wei, Yunyun, He, Dan, Zhao, Busi, Zhang, Xiaowei, Wang, Li. 2022. The sat1 Gene Is Required for the Growth and Virulence of the Human Pathogenic Fungus Aspergillus fumigatus. In Microbiology spectrum, 10, e0155821. doi:10.1128/spectrum.01558-21. https://pubmed.ncbi.nlm.nih.gov/35107385/
4. Kang, Rui, Kroemer, Guido, Tang, Daolin. 2018. The tumor suppressor protein p53 and the ferroptosis network. In Free radical biology & medicine, 133, 162-168. doi:10.1016/j.freeradbiomed.2018.05.074. https://pubmed.ncbi.nlm.nih.gov/29800655/
5. Wan, Kexing, Jia, Min, Zhang, Hong, Liu, Yongmin, Li, Man. 2023. Electroacupuncture Alleviates Neuropathic Pain by Suppressing Ferroptosis in Dorsal Root Ganglion via SAT1/ALOX15 Signaling. In Molecular neurobiology, 60, 6121-6132. doi:10.1007/s12035-023-03463-z. https://pubmed.ncbi.nlm.nih.gov/37421564/
6. Fang, Zhen, Li, Jie, Cao, Feng, Li, Fei. 2022. Integration of scRNA-Seq and Bulk RNA-Seq Reveals Molecular Characterization of the Immune Microenvironment in Acute Pancreatitis. In Biomolecules, 13, . doi:10.3390/biom13010078. https://pubmed.ncbi.nlm.nih.gov/36671463/
7. Zhao, Chunyuan, Ma, Yunjin, Zhang, Minghui, Gao, Chengjiang, Zhao, Wei. 2023. Polyamine metabolism controls B-to-Z DNA transition to orchestrate DNA sensor cGAS activity. In Immunity, 56, 2508-2522.e6. doi:10.1016/j.immuni.2023.09.012. https://pubmed.ncbi.nlm.nih.gov/37848037/
8. Tian, Wenwen, Zhu, Lewei, Luo, Yongzhou, Xie, Xiaoming, Ye, Feng. 2024. Autophagy Deficiency Induced by SAT1 Potentiates Tumor Progression in Triple-Negative Breast Cancer. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2309903. doi:10.1002/advs.202309903. https://pubmed.ncbi.nlm.nih.gov/39073262/
9. Chen, Haoyan, Tong, Tianying, Lu, Shi-Yuan, Hong, Jie, Fang, Jing-Yuan. 2023. Urea cycle activation triggered by host-microbiota maladaptation driving colorectal tumorigenesis. In Cell metabolism, 35, 651-666.e7. doi:10.1016/j.cmet.2023.03.003. https://pubmed.ncbi.nlm.nih.gov/36963394/
10. Dang, Yini, He, Qing, Yang, Siyu, Zheng, Yu, Wu, Ting. 2022. FTH1- and SAT1-Induced Astrocytic Ferroptosis Is Involved in Alzheimer's Disease: Evidence from Single-Cell Transcriptomic Analysis. In Pharmaceuticals (Basel, Switzerland), 15, . doi:10.3390/ph15101177. https://pubmed.ncbi.nlm.nih.gov/36297287/