Arf3-flox Mouse

Arf3, short for ADP-ribosylation factor 3, is a gene involved in diverse biological processes. It encodes a small GTPase that regulates Golgi dynamics, which is crucial for vesicle biogenesis, trafficking, and signaling via the Endoplasmic reticulum-Golgi network [2]. This process supports essential developmental processes and its disruption can lead to various disorders. Arf3 also participates in regulating key cell-signaling pathways such as AKT and ERK, which are important for cell proliferation, apoptosis, and cell-cycle regulation [1].

In cancer research, functional experiments in gastric cancer cells showed that Arf3 inhibits proliferation, induces cell-cycle arrest, and enhances apoptosis by regulating the AKT and ERK pathway [1]. In prostate cancer, ARF3 controls the modality of invasion, acting as a switch between leader cell-led chains of invasion or collective sheet movement by regulating N-cadherin levels, and its levels act as a rheostat for metastasis [4]. In osteosarcoma, circ_ARF3, a circular RNA related to Arf3, sponges miR-1299 to maintain CDK6 expression, promoting the pathogenesis of osteosarcoma [3].

In neurodevelopmental disorders, de novo missense variants in ARF3 can disrupt Golgi integrity and cause a developmental disease impairing nervous system and skeletal formation [2]. In zebrafish, disease modeling validates the dominant behavior of the mutants and their differential impact on brain and body plan formation [2]. In two unrelated children with de novo pathogenic variants in the ARF3 gene, in vitro and in vivo studies revealed that these variants impair the Golgi transport system, leading to different clinical features such as diffuse brain atrophy and cerebellar hypoplasia [5].

In conclusion, Arf3 plays a significant role in multiple biological processes and diseases. Its functions range from regulating cell proliferation, apoptosis, and cell-cycle in cancer to maintaining Golgi integrity and normal development in the nervous system and skeletal formation. Studies using cell lines, animal models like zebrafish, and patient samples have provided insights into its functions, which can potentially contribute to the understanding of disease mechanisms and the development of therapeutic strategies for related diseases such as cancer and neurodevelopmental disorders.