Rbpj-flox Mouse

Rbpj, also known as Recombination signal-binding protein for immunoglobulin kappa J region, is a crucial transcriptional regulator. It is the central player in the Notch signaling pathway. In the Notch cascade, it either forms an activator complex with the Notch intracellular domain (NICD) or a repressor complex with corepressors, and this balance is determined by the Notch receptor's activation state. Rbpj is vital for maintaining immune homeostasis and is involved in many biological processes [2,4].

In pancreatic cancer, conditional transgenic mouse models (Ptf1α-CreERT-driven) showed that RBPJ deficiency in adult pancreatic acinar cells doesn't affect their homeostasis but sensitizes them to KRAS-mediated pancreatic intraepithelial neoplasia initiation, promoting fibrotic stroma formation [1].

In epithelial ovarian cancer, deletion of Rbpj in endothelial cells of adult mice reduced monocyte-derived macrophage infiltration into the tumor microenvironment, affecting tumor-associated macrophage (TAM) education and EOC progression [3].

In brain arteriovenous malformation (bAVM) mouse models, deletion of endothelial Rbpj normalized Notch4-induced bAVM, and in an in vivo mouse model of Rbpj-mediated bAVM, Rbpj deficiency disrupted vascular remodeling via abnormal Apelin and Cdc42 activity [5,9].

In uveitis, targeted RBPJ knockdown in rats promoted M2 macrophage polarization through the mtROS-mediated Notch1-Jagged1-Hes1 signaling pathway, ameliorating uveitis [7].

In metabolic dysfunction-associated steatotic liver disease, Rbpj deficiency in mice blunted inflammatory macrophages and monocyte-derived KC differentiation, promoting protective Ly6Clo monocytes [8].

In T-cell fate regulation, targeting RBPJ enhanced functional and epigenetic reprogramming of Tex cells, improving antitumour effects [6].

In conclusion, Rbpj plays essential roles in multiple biological processes mainly through its function in the Notch signaling pathway. Gene knockout and conditional knockout mouse models have significantly contributed to understanding its role in diseases such as pancreatic cancer, epithelial ovarian cancer, bAVM, uveitis, metabolic-associated liver disease, and cancer immunotherapy. These studies provide insights into potential therapeutic strategies targeting Rbpj in these disease areas.