P4ha1-flox 基因敲除小鼠

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产品名称

P4ha1-flox 基因敲除小鼠

产品编号

S-CKO-18802

品系全称

C57BL/6JCya-P4ha1em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-18451-P4ha1-B6J-VB

品系状态

使用本品系发表的文献需注明: P4ha1-flox 基因敲除小鼠 mice (Strain S-CKO-18802) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
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
procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha 1 polypeptide
基因别称
P4ha
染色体号
Chr 10 (Mouse)
转录本 ID
NCBI: NM_011030 | Ensembl: ENSMUST00000009789
修饰方式
条件性基因敲除
靶向范围
Exon 3
敲除长度
~1.6 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:97463Mice homozygous for a null mutation display embryonic lethality during organogenesis, capillary ruptures, and impaired basement membrane formation.
P4HA1,也称为脯氨酰-4-羟化酶亚基α1,是一种重要的酶,属于脯氨酰-4-羟化酶(P4H)家族,主要负责胶原蛋白的脯氨酸残基的羟基化过程。胶原蛋白是结缔组织的主要成分,其稳定性和功能对于维持组织结构和功能至关重要。P4HA1的活性对于胶原蛋白的正确折叠和成熟至关重要,其功能障碍可能导致多种疾病,如骨质疏松症、皮肤松弛和心血管疾病[1]。

P4HA1在缺氧条件下表达上调,这与其在肿瘤发生发展中的作用密切相关。在缺氧环境下,肿瘤细胞通过增加糖酵解来满足其能量需求,而P4HA1在这个过程中发挥重要作用。P4HA1通过调节α-酮戊二酸(α-KG)水平,进而影响DNA去甲基化酶TET2的表达和活性,最终导致糖酵解相关基因FBP1的表达下调,从而增强内皮细胞糖酵解代谢,促进血管生成,有利于肿瘤的生长和转移[2]。

此外,P4HA1还参与其他生物学过程,如炎症反应、细胞凋亡和细胞周期调控等。P4HA1在多种肿瘤中表达上调,如胶质母细胞瘤、口腔鳞状细胞癌、非酒精性脂肪肝疾病和鼻咽癌等,并与患者的预后不良相关[3,4,5,6,7,8,9,10]。因此,P4HA1可能成为肿瘤治疗的新靶点。

综上所述,P4HA1是一种重要的酶,参与胶原蛋白的羟基化过程,其活性对于维持组织结构和功能至关重要。P4HA1在缺氧条件下表达上调,通过调节糖酵解代谢,促进血管生成,有利于肿瘤的生长和转移。此外,P4HA1还参与其他生物学过程,如炎症反应、细胞凋亡和细胞周期调控等。P4HA1在多种肿瘤中表达上调,并与患者的预后不良相关。因此,P4HA1可能成为肿瘤治疗的新靶点。

参考文献:
1. Xu, Yating, Xia, Di, Huang, Kai, Liang, Minglu. 2024. Hypoxia-induced P4HA1 overexpression promotes post-ischemic angiogenesis by enhancing endothelial glycolysis through downregulating FBP1. In Journal of translational medicine, 22, 74. doi:10.1186/s12967-024-04872-x. https://pubmed.ncbi.nlm.nih.gov/38238754/
2. Yang, Shixue, Zhan, Qi, Su, Dongyuan, Yang, Eryan, Kang, Chunsheng. . HIF1α/ATF3 partake in PGK1 K191/K192 succinylation by modulating P4HA1/succinate signaling in glioblastoma. In Neuro-oncology, 26, 1405-1420. doi:10.1093/neuonc/noae040. https://pubmed.ncbi.nlm.nih.gov/38441561/
3. Kappler, Matthias, Kotrba, Johanna, Kaune, Tom, Eckert, Alexander W, Vordermark, Dirk. 2017. P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients. In Clinical and translational radiation oncology, 5, 6-11. doi:10.1016/j.ctro.2017.05.002. https://pubmed.ncbi.nlm.nih.gov/29594211/
4. Cao, Jiali, Zhong, Qiangqiang, Huang, Yumei, Wang, Ziwen, Xiong, Zhifan. 2023. Identification and validation of INHBE and P4HA1 as hub genes in non-alcoholic fatty liver disease. In Biochemical and biophysical research communications, 686, 149180. doi:10.1016/j.bbrc.2023.149180. https://pubmed.ncbi.nlm.nih.gov/37922570/
5. Zhou, Rui, Qiu, Lin, Zhou, Ling, Yang, Shiping, Wu, Jiangxue. 2023. P4HA1 activates HMGCS1 to promote nasopharyngeal carcinoma ferroptosis resistance and progression. In Cellular signalling, 105, 110609. doi:10.1016/j.cellsig.2023.110609. https://pubmed.ncbi.nlm.nih.gov/36702290/
6. Zhang, Jun, Lyu, Zhuwan, Li, Bo, Xiao, Xiao, Ma, Xiong. 2023. P4HA2 induces hepatic ductular reaction and biliary fibrosis in chronic cholestatic liver diseases. In Hepatology (Baltimore, Md.), 78, 10-25. doi:10.1097/HEP.0000000000000317. https://pubmed.ncbi.nlm.nih.gov/36799463/
7. Chen, Zhangxing, Chen, Meiyan, Xue, Zengyan, Zhu, Xiaosan. 2021. Comprehensive Analysis of Gene Expression Profiles Identifies a P4HA1-Related Gene Panel as a Prognostic Model in Colorectal Cancer Patients. In Cancer biotherapy & radiopharmaceuticals, 36, 693-704. doi:10.1089/cbr.2021.0242. https://pubmed.ncbi.nlm.nih.gov/34520234/
8. Gou, Wenbin, Song, Beiwen, Yang, Yongqiang. . P4HA1 expression and function in esophageal squamous cell carcinoma. In Medicine, 102, e36800. doi:10.1097/MD.0000000000036800. https://pubmed.ncbi.nlm.nih.gov/38134053/
9. Wu, Changwu, Gong, Siming, Duan, Yingjuan, Osterhoff, Georg, Schopow, Nikolas. 2023. A tumor microenvironment-based prognostic index for osteosarcoma. In Journal of biomedical science, 30, 23. doi:10.1186/s12929-023-00917-3. https://pubmed.ncbi.nlm.nih.gov/37055822/
10. Jiang, Hua, Hu, Yang, Zhang, Zhibo, Chen, Xujia, Gao, Jianpeng. 2023. Identification of metabolic biomarkers associated with nonalcoholic fatty liver disease. In Lipids in health and disease, 22, 150. doi:10.1186/s12944-023-01911-2. https://pubmed.ncbi.nlm.nih.gov/37697333/