C57BL/6JCya-Pbrm1em1flox/Cya
Common Name:
Pbrm1-flox
Product ID:
S-CKO-13389
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Pbrm1-flox
Strain ID
CKOCMP-66923-Pbrm1-B6J-VA
Gene Name
Product ID
S-CKO-13389
Gene Alias
2610016F04Rik; BAF180; Pb1
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
14
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Pbrm1em1flox/Cya mice (Catalog S-CKO-13389) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000112098
NCBI RefSeq
NM_001081251
Target Region
Exon 5
Size of Effective Region
~0.6 kb
Detailed Document
Overview of Gene Research
Pbrm1, encoding polybromo-1, is a subunit of the PBAF chromatin remodeling complex. It plays crucial roles in chromatin modification and remodeling, which are essential for regulating gene expression, maintaining genomic stability, and influencing multiple biological processes and disease-related pathways [1,3,4,7,8]. It is associated with pathways like NF-κB, and its functions are vital in normal development and disease prevention. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.
In mouse models, conditional ablation of Pbrm1 in uterine stromal cells disrupts progesterone pathways and uterine receptivity, preventing embryo implantation as it compromises Hand2 transcription and stromal-epithelial crosstalk [2]. In clear cell renal cell carcinoma (ccRCC), Pbrm1 deficiency leads to ectopic PBAF complexes, activating the pro-tumorigenic NF-κB pathway [3]. Also, Pbrm1-deficient cancers show synthetic lethality with PARP and ATR inhibitors due to elevated replication stress and R-loops [4]. In ccRCC, Pbrm1 mutations are associated with increased hERV expression in a HIF-dependent manner [5]. And Pbrm1-deficient renal cancer cells are sensitive to DNMT inhibitor 5-Fluoro-2'-Deoxycytidine [6].
In conclusion, Pbrm1 is essential for chromatin-related functions, influencing processes like embryo implantation and playing a significant role in diseases, especially ccRCC. Mouse KO/CKO models have been instrumental in revealing its functions in these specific biological and disease contexts, providing insights into potential therapeutic strategies for related diseases.
References:
1. Walton, Joseph, Lawson, Keith, Prinos, Panagiotis, Arrowsmith, Cheryl, Ailles, Laurie. 2022. PBRM1, SETD2 and BAP1 - the trinity of 3p in clear cell renal cell carcinoma. In Nature reviews. Urology, 20, 96-115. doi:10.1038/s41585-022-00659-1. https://pubmed.ncbi.nlm.nih.gov/36253570/
2. Xin, Qiliang, Feng, Iris, Yu, Guoyun, Dean, Jurrien. 2024. Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in the mouse uterus. In The Journal of clinical investigation, 134, . doi:10.1172/JCI174194. https://pubmed.ncbi.nlm.nih.gov/38426493/
3. Yao, Xiaosai, Hong, Jing Han, Nargund, Amrita M, Tan, Patrick, Teh, Bin Tean. 2023. PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma. In Nature cell biology, 25, 765-777. doi:10.1038/s41556-023-01122-y. https://pubmed.ncbi.nlm.nih.gov/37095322/
4. Chabanon, Roman M, Morel, Daphné, Eychenne, Thomas, Lord, Christopher J, Postel-Vinay, Sophie. . PBRM1 Deficiency Confers Synthetic Lethality to DNA Repair Inhibitors in Cancer. In Cancer research, 81, 2888-2902. doi:10.1158/0008-5472.CAN-21-0628. https://pubmed.ncbi.nlm.nih.gov/33888468/
5. Zhou, Mi, Leung, Janet Y, Gessner, Kathryn H, Davis, Ian J, Kim, William Y. . PBRM1 Inactivation Promotes Upregulation of Human Endogenous Retroviruses in a HIF-Dependent Manner. In Cancer immunology research, 10, 285-290. doi:10.1158/2326-6066.CIR-21-0480. https://pubmed.ncbi.nlm.nih.gov/35013001/
6. Gu, Di, Dong, Kai, Jiang, Aimin, Yang, Chenghua, Wang, Linhui. 2022. PBRM1 Deficiency Sensitizes Renal Cancer Cells to DNMT Inhibitor 5-Fluoro-2'-Deoxycytidine. In Frontiers in oncology, 12, 870229. doi:10.3389/fonc.2022.870229. https://pubmed.ncbi.nlm.nih.gov/35719970/
7. De Silva, Saumya M, Dhiman, Alisha, Sood, Surbhi, Dykhuizen, Emily C, Musselman, Catherine A. . PBRM1 bromodomains associate with RNA to facilitate chromatin association. In Nucleic acids research, 51, 3631-3649. doi:10.1093/nar/gkad072. https://pubmed.ncbi.nlm.nih.gov/36808431/
8. Zimmer, Kai, Kocher, Florian, Untergasser, Gerold, Widmann, Gerlig, Seeber, Andreas. 2023. PBRM1 mutations might render a subtype of biliary tract cancers sensitive to drugs targeting the DNA damage repair system. In NPJ precision oncology, 7, 64. doi:10.1038/s41698-023-00409-5. https://pubmed.ncbi.nlm.nih.gov/37400502/
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