Pofut1-flox Mouse

POFUT1, Protein O-fucosyltransferase 1, is mainly responsible for O-fucosylated glycan biosynthesis on glycoproteins. It is an essential regulator of NOTCH signaling, which is involved in numerous biological processes like cell differentiation, development, and disease occurrence [2,3,4,5,9].

In endothelial-specific Pofut1 knockout mice, POFUT1 loss promoted injury-induced liver sinusoidal endothelial cell (LSEC) capillarization and hepatic stellate cell (HSC) activation, leading to aggravated liver fibrosis. Mechanistically, it augmented fibrinogen expression by enhancing NOTCH/HES1/STAT3 signaling [1]. In trophoblast cells, poFUT1 deficiency led to fewer blood vessels in villi and decidua, and its overexpression promoted cell proliferation, migration, and angiogenesis potential [2]. In glioblastoma cells, knockdown of POFUT1 inhibited cell proliferation and invasion, while overexpression potentiated these abilities through Notch signaling activation [3]. In gastric cancer cells, POFUT1 promoted proliferation, metastasis, and inhibited apoptosis through Notch/Wnt dual signaling pathways [4]. In endometrial stromal cells, poFUT1 promoted decidualization by enhancing the O-fucosylation of Notch1 [5]. In colorectal cancer cells, silencing of POFUT1 decreased proliferation, migration, and increased apoptosis [6,9]. In muscle-invasive bladder cancer, low levels of POFUT1 mRNA were an independent prognostic indicator for overall and cancer-specific survival after radical cystectomy [7]. In mouse podocytes, POFUT1 was dispensable for structure, function, and survival [8].

In conclusion, POFUT1 plays crucial roles in multiple biological processes and diseases, mainly through its regulation of NOTCH signaling. Gene knockout and conditional knockout mouse models have been instrumental in revealing its functions in liver fibrosis, placental angiogenesis, cancer development, and other disease-related processes, providing potential therapeutic targets for these diseases.