Khdrbs1-flox Mouse

KHDRBS1, also known as Sam68, is an RNA-binding protein that plays crucial roles in multiple biological processes. It is involved in signal transduction and is associated with pathways such as NF-κB activation, which is important for cellular responses to DNA damage [3,5]. It also has a connection with the regulation of RNA stability and gene expression, influencing various biological functions [1,2]. Genetic models, like those in zebrafish, have been valuable in studying its functions [4].

In a zebrafish model of severe liver injury, khdrbs1 was found to be specifically expressed in bipotential progenitor cells (BPPCs). Loss-of-function experiments in zebrafish, using a CRISPR/dead Cas9-mediated system to interfere with khdrbs1 in biliary epithelial cells, led to defective liver regeneration and impaired re-differentiation of BPPCs. The khdrbs1-/-mutant showed impaired proliferation and re-differentiation of BPPCs, and this was associated with the activation of p53 signaling, as tp53 mutation could partially rescue the defective liver regeneration of the khdrbs1-/-mutant [4]. In mouse models, Sam68/KHDRBS1 deficiency abolished DNA damage-stimulated polymers of ADP-ribose (PAR) production and the PAR-dependent NF-κB transactivation of anti-apoptotic genes. Sam68 deleted cells were hypersensitive to genotoxicity, and knockdown of Sam68 sensitized human colon cancer cells to genotoxic stress-induced apoptosis, while genetic deletion of Sam68 dampened colon tumor burden in mice, indicating its role in colon tumorigenesis [5].

In conclusion, KHDRBS1 is essential for processes like liver regeneration in zebrafish and plays a significant role in colon tumorigenesis in mice. Its functions are mainly related to the regulation of cell-related processes such as re-differentiation, proliferation, and responses to genotoxic stress through its influence on signaling pathways like p53 and NF-κB. The use of gene-knockout models in zebrafish and mice has provided crucial insights into its role in these specific biological and disease-related processes.