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. This study comprised of 3 conditions (homozygotes, heterozygotes, and wild-type littermates) with 4 replicates in each. The RNA was extracted from kidney cortex homogenates of the rats. contributor: Genomic Sciences and Precision Medicine Center at the Medical College of Wisconsin