Lack of xanthine dehydrogenase leads to a remarkable renal decline in a novel hypouricemic rat model

The SSXdh-/- rat (SS-Xdhem1Mcwi, Rat Genome Database ID:14398479), created on the Dahl SS background, resulted in severe hypouricemia in the tissues. With the Xdh project, the overall hypothesis is that the Xdh gene ablation will result in kidney damage and perturbation of blood pressure control. We were interested in finding out if the gene ablation alternates the kidney development process. The deletion of Xdh protein produced dramatic changes in proteins related to the salvage pathway. The novel Xdh knockout rat model exhibited profound hypouricemia, which increased oxidative stress and crystal formation, leading to inflammation, renal cell proliferation, severe kidney damage, and a subsequent decline in renal function.本数据集所依托的SSXdh基因敲除大鼠（SS-Xdhem1Mcwi，大鼠基因组数据库编号：14398479）以Dahl SS大鼠为遗传背景构建，可导致机体组织出现严重低尿酸血症。本次Xdh相关研究的核心假说为：敲除Xdh基因将引发肾脏损伤，并干扰血压调控机制。本研究旨在探究该基因敲除是否会改变肾脏发育进程。Xdh蛋白的缺失会使嘌呤补救合成途径相关蛋白发生显著改变。该新型Xdh基因敲除大鼠模型表现出显著的低尿酸血症，该病症会加剧氧化应激与晶体形成，进而引发炎症反应、肾细胞增殖、严重肾脏损伤，并最终导致肾功能下降。