Bap1-flox Mouse

BAP1, short for BRCA1-Associated Protein 1, is a ubiquitin carboxy-terminal hydrolase functioning as a tumor suppressor. It utilizes its deubiquitinating activity to regulate multiple processes such as DNA damage repair, cell cycle control, chromatin modification, programmed cell death, and the immune response [1,3,4,6]. It is also involved in metabolic regulation of ferroptosis, an important non-apoptotic form of cell death [2].

In normal human cholangiocyte organoids, CRISPR-Cas9-induced BAP1 loss-of-function led to loss of epithelial characteristics and increased motility, with restoration of BAP1's catalytic activity in the nucleus rescuing these changes. In a genetic background of human liver organoids engineered with four common cholangiocarcinoma mutations, BAP1 loss resulted in acquisition of malignant features upon xenotransplantation [5].

In conclusion, BAP1 is crucial for maintaining normal cellular functions through its regulation of diverse biological processes. The use of genetic models like CRISPR-engineered organoids has revealed its significance in tumor suppression, especially in cancers such as cholangiocarcinoma. Germline BAP1 mutations are associated with a high risk of developing multiple cancers, defining the "BAP1 cancer syndrome" [3,4,7].