Usp45-flox Mouse

Usp45, a ubiquitin-specific protease, is involved in multiple biological processes. It functions as a deubiquitinating enzyme, removing ubiquitin molecules from target proteins, thus regulating protein degradation. It is associated with pathways like DNA repair, cell migration, and autophagy, and is of great biological importance in processes such as tumorigenesis, retinal development, and cell division [1-10]. Genetic models, including knockout mouse models, have been crucial in studying its functions.

In serous ovarian cancer, knockdown of MYH10, which recruits USP45 in combination with MYH9, suppresses cell proliferation, migration, invasion, metastasis, and cisplatin resistance, indicating USP45's role in promoting tumorigenesis in this cancer type [1]. In pan-cancer analysis, USP45 is upregulated in most tumors, negatively correlated with patient survival, and its structural and copy-number variations are identified. It is also related to mRNA methylation, tumor heterogeneity, stemness, and immune regulation [2]. In DNA repair, USP45 knockout cells are hypersensitive to UV irradiation and DNA inter-strand cross-links, with reduced repair of UV-induced DNA damage due to impaired ERCC1 translocation [3]. In zebrafish, knockdown of usp45 leads to abnormal retinal development, and knockout of Usp45 in mice causes abnormal electroretinography responses, similar to patients with Leber congenital amaurosis, suggesting its importance in photoreceptor function [4].

In conclusion, USP45 plays essential roles in DNA repair, cell migration, autophagy, tumorigenesis, and retinal development. Model-based research, especially Usp45 knockout mouse models, has significantly contributed to understanding its functions in diseases such as cancer and Leber congenital amaurosis, providing potential therapeutic targets for these diseases.