Pbrm1-flox Mouse

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.