Uxs1-KO Mouse

Uxs1, or UDP-glucuronate decarboxylase 1, is a Golgi enzyme that converts UDP-glucuronic acid (UDPGA) to UDP-xylose. This conversion is crucial in the sugar nucleotide biosynthetic pathway, and Uxs1 also limits UDPGA production through negative feedback on UGDH, the enzyme immediately upstream of it [2].

In a study on choroidal neovascularization (CNV), a novel circRNA, circRNA Uxs1, was identified. It was upregulated in CNV patient specimens and CNV mouse models. Knockdown of circRNA Uxs1 interrupted endothelial cell tube formation, migration, and proliferation in vitro, and alleviated neovascularization in vivo by sponging miR-335-5p, which activated the mTOR/p70 S6k pathway via upregulating PGF expression [1].

In zebrafish, a mutation in uxs1 led to a lack of proteoglycan-rich extracellular matrix in craniofacial cartilages, defective chondrocyte organization, and disrupted gene expression related to skeletal development, indicating its essential role in skeletal extracellular matrix production and organization [3].

In cryptococci, uxs1 mutants accumulated UDP-glucuronic acid, down-regulated the expression of permease FCY2, and reduced cellular uptake of 5-fluorocytosine, contributing to drug resistance [4].

In summary, Uxs1 is essential for processes such as sugar nucleotide metabolism, CNV regulation, skeletal development, and drug resistance in fungi. Studies using gene-knockdown models in mice and zebrafish, as well as mutant models in fungi, have revealed its role in these biological processes and disease-related conditions, providing insights into potential therapeutic targets for CNV and understanding the mechanisms of skeletal development and drug resistance [1,3,4].