Adgrf5-flox Mouse

Adgrf5, also known as GPR116 and Ig-Hepta, is an adhesion G-protein-coupled receptor (GPCR). It plays essential roles in various physiological processes, such as maintaining the integrity of the glomerular filtration barrier, regulating gene expression related to the glomerular basement membrane and a mechanosensitive transcription factor [1]. It is also involved in processes like breast cancer progression, angiogenesis in the retina, renal acid secretion, pancreatic islet function, and may be related to peri-implant fibrosis [2,3,4,5,6].

Deletion of Adgrf5 in mice led to abnormal structural and functional properties of the glomerular filtration barrier, with defects like albuminuria, kidney function impairment, and morphological changes in the glomeruli, along with altered gene expression of glomerular basement membrane components and Klf2 in glomerular endothelial cells [1]. In breast cancer cells, absence of Adgrf5 impaired cell motility and tumor growth, correlating with increased MMP8 expression and a shift in tumor-associated neutrophil polarization [2]. In Adgrf5 mutant mouse retinae, there were vascular morphogenetic defects including increased vascular density in perivenous areas and transient vascular protrusions in the inner retinal space [3]. Kidney-specific knockout of Adgrf5 (Gpr116) caused a significant reduction in urine pH, accompanied by blood pH increase and pCO2 decrease, suggesting its role in regulating V-ATPase trafficking and urinary acidification [4]. Whole-body Gpr116 deficiency in mice led to changes in pancreatic islet development, such as decreased beta-cell mass and lower number of small islets, along with an impact on glucose homeostasis [5]. Conditional deletion of Adgrf5 in LEPR+ cells attenuated peri-implant fibrosis while augmenting peri-implant bone formation in a mouse model [6].

In conclusion, Adgrf5 is crucial for normal physiological functions in multiple organs including the kidney, pancreas, and retina. Gene knockout mouse models have revealed its significant roles in diseases such as glomerular disorders, breast cancer, and peri-implant fibrosis. Understanding Adgrf5 function through these models provides potential insights into disease mechanisms and possible therapeutic targets for these conditions.