Dock4, a guanine nucleotide exchange factor, is crucial for regulating the activity of small GTPases like Rac1. It is involved in multiple biological processes including cell adhesion, migration, and differentiation. The Dock4-Rac1 pathway plays a significant role in maintaining normal physiological functions and is associated with various diseases [1-10]. Genetic models, such as gene knockout mouse models, have been instrumental in studying its functions.

In Dock4 null mice, there is a significant decrease in gastric ghrelin production, indicating Dock4's role in regulating this hunger-related hormone [1]. Dock4-deficient mice show lung-specific hemorrhage, increased basal microvascular permeability, and impaired response to S1P-induced reversal of thrombin-induced permeability, suggesting its importance in maintaining lung vascular barrier function [2]. In Dock4 gene knockout mice, there are disordered intestinal epithelium, shortage of goblet cells, and low expression of MUC2, demonstrating its role in goblet cell differentiation and MUC2 production in the intestine [3]. Dock4 knockdown mice display significant hearing impairment, hair bundle deficits, increased oxidative stress, and eventually cochlear hair cell apoptosis, highlighting its critical role in the maintenance of auditory hair cells and hearing function [4].

In conclusion, Dock4 plays essential roles in multiple biological processes including hormone regulation, vascular barrier maintenance, intestinal epithelial function, and hearing. Studies using KO mouse models have significantly contributed to understanding its roles in these processes and related disease areas such as atherosclerosis, gastric function-related disorders, pulmonary diseases, intestinal disorders, and hearing-related problems.