Art3-KO Mouse

Art3, also known as human ecto-ADP-ribosyltransferase 3, is involved in multiple biological functions. It can regulate cell function through activation of pathways like Akt and ERK. In the context of phospholipid homeostasis, it impacts the trafficking of the glycerophosphoinositol transporter Git1, playing a role in controlling phospholipid distribution. Additionally, it has been associated with spermatogenesis and cell-cycle-related processes such as DNA-repair and regulation of the inflammatory response [1,2,3,5,6].

In triple-negative breast cancer (TNBC), overexpression of Art3 in MDA-MB-231 cells increased cell proliferation, invasion, survival in vitro, and growth of xenograft tumors, while knockdown inhibited these functions. Art3 overexpression also activated AKT and ERK in vitro and in xenograft tumors, suggesting it is a critical TNBC marker [1]. In yeast, disruption of the ART3 gene was defective in the arginine-induced endocytosis of the high-affinity proline transporter Put4, indicating Art3 is a key regulator for this process [4]. In the Chinese population, an SNP (rs6836703) in the intron11 region of Art3 gene was significantly associated with male infertility [3]. In a rat traumatic brain injury model, the expression of Art3 in the ipsilateral brain cortex increased, peaking at day 3 post-injury, and was mainly localized in the plasmalemma of neurons [6]. Maternal folate depletion was significantly associated with Art3 gene hypomethylation in subcortical brain tissue of adult mice [7].

In summary, Art3 is crucial in multiple biological processes and disease conditions. Its role in TNBC, male infertility, and brain injury pathophysiology, as well as its connection to phospholipid homeostasis and spermatogenesis, has been revealed through various in vitro and in vivo studies. These findings contribute to our understanding of the underlying mechanisms in these disease areas and biological functions.