C57BL/6JCya-Toporsem1/Cya
Common Name:
Topors-KO
Product ID:
S-KO-00433
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Topors-KO
Strain ID
KOCMP-106021-Topors-B6J-VA
Gene Name
Product ID
S-KO-00433
Gene Alias
LUN; TP53BPL; p53BP3; p53BP3/LUN
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
4
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Toporsem1/Cya mice (Catalog S-KO-00433) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000042575
NCBI RefSeq
NM_134097
Target Region
Exon 3
Size of Effective Region
~2.7 kb
Detailed Document
Overview of Gene Research
TOPORS, also known as topoisomerase I-binding arginine/serine-rich protein, functions as an E3 ubiquitin and SUMO1 ligase. It is involved in DNA-protein crosslink (DPC) repair, homologous recombination repair, and maintaining higher-order chromatin architecture. These functions are crucial for normal cellular processes, and its dysregulation may lead to various diseases [4,7,8].
Genome-wide CRISPR-Cas9 screens have identified TOPORS as a gene whose loss-of-function synergizes with hypomethylating agents (HMAs) in acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) cells. Depletion of TOPORS makes leukemic blasts sensitive to HMAs by impairing the DNA damage response and accumulating SUMOylated DNMT1 [1,5]. In the context of decitabine treatment for hematological cancers, TOPORS is a DPC repair factor, and its loss promotes cytotoxicity [2]. Additionally, in Joubert syndrome, a missense variant in TOPORS has been identified in individuals of Dominican descent, nominating it as a novel causal gene [3]. Mutations in TOPORS have also been detected in families with retinitis pigmentosa, expanding the understanding of its genotype-phenotype correlations [6].
In conclusion, TOPORS is essential for DNA repair, chromatin architecture, and normal cellular function. Loss-of-function studies, such as those using CRISPR-Cas9, have revealed its role in drug resistance in AML and MDS, as well as its association with ciliopathy-spectrum diseases like Joubert syndrome and retinitis pigmentosa. These findings provide valuable insights into disease mechanisms and potential therapeutic strategies.
References:
1. Truong, Peter, Shen, Sylvie, Joshi, Swapna, Jolly, Christopher J, Pimanda, John E. 2024. TOPORS E3 ligase mediates resistance to hypomethylating agent cytotoxicity in acute myeloid leukemia cells. In Nature communications, 15, 7360. doi:10.1038/s41467-024-51646-6. https://pubmed.ncbi.nlm.nih.gov/39198401/
2. Carnie, Christopher J, Götz, Maximilian J, Palma-Chaundler, Chloe S, Stingele, Julian, Jackson, Stephen P. 2024. Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS. In The EMBO journal, 43, 2397-2423. doi:10.1038/s44318-024-00108-2. https://pubmed.ncbi.nlm.nih.gov/38760575/
3. Strong, Alanna, Qu, Hui-Qi, Cullina, Sinéad, Kenny, Eimear E, Hakonarson, Hakon. 2023. TOPORS as a novel causal gene for Joubert syndrome. In American journal of medical genetics. Part A, 191, 2156-2163. doi:10.1002/ajmg.a.63303. https://pubmed.ncbi.nlm.nih.gov/37227088/
4. Hariharasudhan, Gurusamy, Jeong, Seo-Yeon, Kim, Min-Ji, You, Ho Jin, Lee, Jung-Hee. . TOPORS-mediated RAD51 SUMOylation facilitates homologous recombination repair. In Nucleic acids research, 50, 1501-1516. doi:10.1093/nar/gkac009. https://pubmed.ncbi.nlm.nih.gov/35061896/
5. Kaito, Satoshi, Aoyama, Kazumasa, Oshima, Motohiko, Nakanishi, Makoto, Iwama, Atsushi. 2024. Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization. In Nature communications, 15, 7359. doi:10.1038/s41467-024-50498-4. https://pubmed.ncbi.nlm.nih.gov/39198387/
6. He, Kaiwen, Zhou, Yunyu, Li, Ningdong. 2022. Mutations of TOPORS identified in families with retinitis pigmentosa. In Ophthalmic genetics, 43, 371-377. doi:10.1080/13816810.2022.2039721. https://pubmed.ncbi.nlm.nih.gov/35254173/
7. Liu, Julio C Y, Ackermann, Leena, Hoffmann, Saskia, Haahr, Peter, Mailand, Niels. 2024. Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation. In Nature structural & molecular biology, 31, 1355-1367. doi:10.1038/s41594-024-01294-7. https://pubmed.ncbi.nlm.nih.gov/38649616/
8. Ji, Luzhang, Huo, Xiangru, Zhang, Yuwen, Wang, Qianfeng, Wen, Bo. 2020. TOPORS, a tumor suppressor protein, contributes to the maintenance of higher-order chromatin architecture. In Biochimica et biophysica acta. Gene regulatory mechanisms, 1863, 194518. doi:10.1016/j.bbagrm.2020.194518. https://pubmed.ncbi.nlm.nih.gov/32113985/
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