C57BL/6JCya-Usp1em1flox/Cya
Common Name:
Usp1-flox
Product ID:
S-CKO-07336
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Usp1-flox
Strain ID
CKOCMP-230484-Usp1-B6J-VA
Gene Name
Product ID
S-CKO-07336
Gene Alias
--
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
4
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Usp1em1flox/Cya mice (Catalog S-CKO-07336) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000030289
NCBI RefSeq
NM_146144
Target Region
Exon 3~4
Size of Effective Region
~1.6 kb
Detailed Document
Overview of Gene Research
Usp1, or ubiquitin-specific protease 1, is a deubiquitinase enzyme. It plays crucial roles in various biological processes, especially those related to DNA repair, cell cycle regulation, and protein stability. It is involved in pathways such as the homologous-recombination repair pathway and is associated with the regulation of key proteins in multiple signaling cascades. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions [1-10].
In BRCA1-deficient tumors, knockdown or inhibition of Usp1 led to replication fork destabilization and decreased cell viability, uncovering a synthetic lethal relationship. The persistence of monoubiquitinated PCNA at the replication fork was the mechanism of cell death in the absence of Usp1 [1]. In cholangiocarcinoma (CCA), Usp1 promotes progression by deubiquitinating PARP1 to prevent its proteasomal degradation [2]. In hepatocellular carcinoma (HCC), Usp1 modulates progression via the Hippo/TAZ axis by enhancing TAZ stability [3]. In muscle during prolonged starvation, Usp1 deubiquitinates Akt to inhibit PI3K-Akt-FoxO signaling [4]. In cancers with DNA damage vulnerabilities, such as BRCA1/2 mutant tumors, inhibition of Usp1 leads to decreased DNA synthesis and S-phase-specific DNA damage, with the accumulation of ubiquitinated PCNA being a key factor [5]. In CD4+ T-cell differentiation, Usp1 promotes Th17-cell differentiation but attenuates Treg-cell differentiation [6]. In adipocyte differentiation, Usp1 enhances the stability of C/EBPβ, accelerating adipogenesis and lipid accumulation [7]. In HCC, inhibition of Usp1 activates ER stress through ubiquitin-protein aggregation, inducing autophagy and apoptosis [8]. In cancer cells, Usp1 regulates MAST1-driven cisplatin-resistance by stabilizing MAST1 [9]. And the USP1 inhibitor KSQ-4279 can overcome PARP inhibitor resistance in homologous recombination-deficient tumors [10].
In conclusion, Usp1 is a multifunctional deubiquitinase. Its functions span across DNA repair, cancer cell progression, metabolic regulation, and immune cell differentiation. Studies using KO/CKO mouse models have revealed its significance in various disease areas, especially in cancers like BRCA1-deficient tumors, cholangiocarcinoma, and hepatocellular carcinoma. These findings offer potential therapeutic strategies, such as targeting Usp1, for treating related diseases.
References:
1. Lim, Kah Suan, Li, Heng, Roberts, Emma A, Zheng, Ning, D'Andrea, Alan D. . USP1 Is Required for Replication Fork Protection in BRCA1-Deficient Tumors. In Molecular cell, 72, 925-941.e4. doi:10.1016/j.molcel.2018.10.045. https://pubmed.ncbi.nlm.nih.gov/30576655/
2. Zhang, Deng Yong, Zhu, Yan, Wu, Qiong, Kwong, Lawrence N, Lu, Zheng. 2023. USP1 promotes cholangiocarcinoma progression by deubiquitinating PARP1 to prevent its proteasomal degradation. In Cell death & disease, 14, 669. doi:10.1038/s41419-023-06172-6. https://pubmed.ncbi.nlm.nih.gov/37821462/
3. Liu, Dongyi, Li, Quanhui, Zang, Yifeng, Yang, Huijie, Ding, Yinlu. 2023. USP1 modulates hepatocellular carcinoma progression via the Hippo/TAZ axis. In Cell death & disease, 14, 264. doi:10.1038/s41419-023-05777-1. https://pubmed.ncbi.nlm.nih.gov/37041150/
4. Goldbraikh, Dana, Neufeld, Danielle, Eid-Mutlak, Yara, Parnis, Anna, Cohen, Shenhav. 2020. USP1 deubiquitinates Akt to inhibit PI3K-Akt-FoxO signaling in muscle during prolonged starvation. In EMBO reports, 21, e48791. doi:10.15252/embr.201948791. https://pubmed.ncbi.nlm.nih.gov/32133736/
5. Simoneau, Antoine, Engel, Justin L, Bandi, Madhavi, Andersen, Jannik N, Feng, Tianshu. . Ubiquitinated PCNA Drives USP1 Synthetic Lethality in Cancer. In Molecular cancer therapeutics, 22, 215-226. doi:10.1158/1535-7163.MCT-22-0409. https://pubmed.ncbi.nlm.nih.gov/36228090/
6. Zhu, Xiaotong, Wang, Peng, Zhan, Xiaoxia, Jie, Ligang, Hu, Shengfeng. 2023. USP1-regulated reciprocal differentiation of Th17 cells and Treg cells by deubiquitinating and stabilizing TAZ. In Cellular & molecular immunology, 20, 252-263. doi:10.1038/s41423-022-00969-9. https://pubmed.ncbi.nlm.nih.gov/36600049/
7. Kim, Myung Sup, Baek, Jung-Hwan, Lee, JinAh, Lee, Kyeong, Chun, Kyung-Hee. 2023. Deubiquitinase USP1 enhances CCAAT/enhancer-binding protein beta (C/EBPβ) stability and accelerates adipogenesis and lipid accumulation. In Cell death & disease, 14, 776. doi:10.1038/s41419-023-06317-7. https://pubmed.ncbi.nlm.nih.gov/38012162/
8. Wang, Longhao, Hu, Tao, Shen, Zhibo, Chen, Ping, Zhao, Jie. 2022. Inhibition of USP1 activates ER stress through Ubi-protein aggregation to induce autophagy and apoptosis in HCC. In Cell death & disease, 13, 951. doi:10.1038/s41419-022-05341-3. https://pubmed.ncbi.nlm.nih.gov/36357365/
9. Tyagi, Apoorvi, Kaushal, Kamini, Chandrasekaran, Arun Pandian, Kim, Kye-Seong, Ramakrishna, Suresh. 2022. Nuclease technology-based genome-wide screening for deubiquitinase subfamily identifies USP1 regulating MAST1-driven cisplatin-resistance in cancer cells. In Theranostics, 12, 5949-5970. doi:10.7150/thno.72826. https://pubmed.ncbi.nlm.nih.gov/35966591/
10. Cadzow, Louise, Brenneman, Jehrod, Tobin, Erica, Stegmeier, Frank, Wylie, Andrew A. . The USP1 Inhibitor KSQ-4279 Overcomes PARP Inhibitor Resistance in Homologous Recombination-Deficient Tumors. In Cancer research, 84, 3419-3434. doi:10.1158/0008-5472.CAN-24-0293. https://pubmed.ncbi.nlm.nih.gov/39402989/
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