C57BL/6NCya-Top2aem1flox/Cya
Common Name
Top2a-flox
Product ID
S-CKO-06412
Backgroud
C57BL/6NCya
Strain ID
CKOCMP-21973-Top2a-B6N-VA
Status
When using this mouse strain in a publication, please cite “Top2a-flox Mouse (Catalog S-CKO-06412) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
The standard delivery applies for a guaranteed minimum of three heterozygous carriers. Breeding services for homozygous carriers and/or specified sex are available.
Basic Information
Strain Name
Top2a-flox
Strain ID
CKOCMP-21973-Top2a-B6N-VA
Gene Name
Product ID
S-CKO-06412
Gene Alias
Top-2
Background
C57BL/6NCya
Gene Full Name
topoisomerase (DNA) II alpha
Modification
Conditional knockout
NCBI ID
Phenotype
Chromosome
Chr 11 (Mouse)
Application
--
Datasheet
Strain Description
Ensembl Transcript ID
ENSMUST00000068031
NCBI Transcript ID
NM_011623
Target Region
Exon 6~7
Size of Effective Region
~1.8 kb
Overview of Gene Research
Top2a, also known as DNA topoisomerase II alpha, is a key catalytic enzyme in DNA replication and cell proliferation [4]. It is involved in various biological processes and associated with multiple pathways. For instance, it plays a role in resolving topological barriers during replication fork reversal, and is part of the ZATT-TOP2A-PICH axis which promotes genome stability [3].
In ovarian cancer, TOP2A knockdown inhibits cell proliferation, arrests cells in the G1 phase, and induces apoptotic death, and it is confirmed to regulate cell proliferation and cell cycle through the AKT/mTOR pathway [1]. In hepatocellular carcinoma, inhibition of TOP2A and EZH2 induces cellular senescence and inhibits cell proliferation, with EZH2 promoting TOP2A expression by regulating the H3K27me3-mediated epigenetic silencing of miR-139-5p [2]. In medulloblastoma, knockdown of TOP2A inhibits cell proliferation, migration, and invasion, and suppresses radioresistance, with the Wnt/β-catenin signaling pathway potentially involved in its mechanisms [4]. In hepatocellular carcinoma, silencing TOP2A enhances cells' sensitivity to regorafenib, and its inhibition by doxorubicin or epirubicin synergizes with regorafenib to suppress tumor growth [5]. In recurrent implantation failure, TOP2A deficit-induced abnormal decidualization leads to the condition via the NF-κB signaling pathway [6]. In recurrent spontaneous abortion, lower TOP2A expression inhibits trophoblast cell proliferation, migration, and invasion by activating the FOXO signaling pathway, and TOP2A inhibition impairs pre-implantation embryo development in mice [7].
In conclusion, Top2a is essential for DNA replication and cell proliferation. Through gene knockout or knockdown studies in various models, its role in multiple disease conditions such as cancers and reproductive disorders has been revealed. These findings help in understanding the underlying molecular mechanisms and may potentially lead to the development of novel therapeutic strategies targeting Top2a.
References：
1. Zhang, Kaiwen, Zheng, Xingyu, Sun, Yiqing, Tian, Wenyan, Wang, Yingmei. 2024. TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation. In Cancer biology & therapy, 25, 2325126. doi:10.1080/15384047.2024.2325126. https://pubmed.ncbi.nlm.nih.gov/38445610/
2. Wang, Ke, Jiang, Xunliang, Jiang, Yu, Li, Jipeng, Zhang, Rui. 2023. EZH2-H3K27me3-mediated silencing of mir-139-5p inhibits cellular senescence in hepatocellular carcinoma by activating TOP2A. In Journal of experimental & clinical cancer research : CR, 42, 320. doi:10.1186/s13046-023-02855-2. https://pubmed.ncbi.nlm.nih.gov/38008711/
3. Tian, Tian, Bu, Min, Chen, Xu, Li, Qing, Huang, Jun. 2020. The ZATT-TOP2A-PICH Axis Drives Extensive Replication Fork Reversal to Promote Genome Stability. In Molecular cell, 81, 198-211.e6. doi:10.1016/j.molcel.2020.11.007. https://pubmed.ncbi.nlm.nih.gov/33296677/
4. Zhang, Yufeng, Yang, Haiyan, Wang, Liwen, Xiao, Zhiqing, Xue, Xiaoying. 2022. TOP2A correlates with poor prognosis and affects radioresistance of medulloblastoma. In Frontiers in oncology, 12, 918959. doi:10.3389/fonc.2022.918959. https://pubmed.ncbi.nlm.nih.gov/35912241/
5. Wang, Zongwen, Zhu, Qiankun, Li, Xiaodong, Dong, Xiaoqun, Zhai, Bo. 2022. TOP2A inhibition reverses drug resistance of hepatocellular carcinoma to regorafenib. In American journal of cancer research, 12, 4343-4360. doi:. https://pubmed.ncbi.nlm.nih.gov/36225636/
6. Fu, Huijia, Tan, Wang, Chen, Zhi, Qi, Hongbo, Liu, Xiru. 2022. TOP2A deficit-induced abnormal decidualization leads to recurrent implantation failure via the NF-κB signaling pathway. In Reproductive biology and endocrinology : RB&E, 20, 142. doi:10.1186/s12958-022-01013-1. https://pubmed.ncbi.nlm.nih.gov/36138481/
7. Duan, Yuhan, Fu, Huijia, Huang, Jiayu, Liu, Linhong, Liu, Xiru. 2022. TOP2A deficiency leads to human recurrent spontaneous abortion and growth retardation of mouse pre-implantation embryos. In Molecular medicine (Cambridge, Mass.), 28, 165. doi:10.1186/s10020-022-00592-4. https://pubmed.ncbi.nlm.nih.gov/36585615/
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
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