Nup93-KO Mouse

Nup93, a crucial structural protein of the nuclear pore complex (NPC), mediates nucleocytoplasmic shuttling of transcription factors. NPCs play a vital role in controlling the transportation of RNAs, proteins, and other macromolecules between the nucleus and cytoplasm, thereby influencing various biological processes [6,9].

Endothelial Nup93 protein levels decline in aged mice and in vitro models of endothelial aging. Loss of Nup93 impairs NPC transport, leading to nuclear accumulation of Yap and downstream inflammation, suggesting its importance in preventing endothelial cell senescence and vascular aging [1]. In breast cancer, Nup93 depletion reduces cell migration/proliferation, impairs invasion of triple-negative breast cancer cells, and leads to significant defects in tumor establishment/propagation in vivo [2]. In cardiomyocytes, down-regulation of Nup93 aggravates hypoxia-induced injury and cell death through abnormal regulation of gene transcription, mainly affecting oxidative phosphorylation and ribosome subunits-related genes [6]. Mutations in NUP93 cause steroid-resistant nephrotic syndrome in children, with most patients progressing to end-stage kidney disease [3,4,7]. In cervical cancer, knockdown of Nup93 inhibits cell proliferation, migration, and invasion capacity, and prevents tumor formation in mice [8]. In antiviral innate immune responses, Nup93-deficient cells show decreased expression of antiviral genes and impaired IRF3 nuclear translocation, as Nup93 enhances TBK1 activity [5].

In summary, Nup93 is essential for maintaining normal cellular functions. Studies using gene-knockout or other loss-of-function models have revealed its significant roles in various disease conditions such as endothelial cell senescence, breast cancer, cardiomyocyte hypoxia-induced death, steroid-resistant nephrotic syndrome, cervical cancer, and antiviral innate immunity. Understanding Nup93's functions provides potential therapeutic targets for these diseases.