The presence of Xanthine Dehydrogenase is crucial for the maturation of the rat kidneys
We hypothesized that XDH plays a role in nephrogenesis. Here we used SSXdh+/+, SSXdh+/-, and SSXdh-/- rat kidneys from the postnatal development period to test this hypothesis. In wildtype but not homozygote rat kidneys, XDH expression was significantly increased from postnatal day (PND) 5 to 15, indicating its importance in the maturation of the kidney. Even though both genotypes had similar glomerular density at birth, it was significantly lower in SSXdh-/- rats by PND21. Transcriptomic profiling of the kidneys revealed that many genes related to kidney formation were dysregulated by the lack of Xdh expression in this period. Functional and pathway analyses of the transcriptome data strongly suggested that Xdh affected these genes via epidermal growth factor (EGF) signaling disruption. This study showed that Xdh is essential for the kidney maturation process. Overall design: All animals used for the current study were male. The pups were euthanized by decapitation under deep anesthesia (2%–3 % (vol/vol) isoflurane), and both kidneys were collected. One kidney was stored in Formalin for histological analyses, and the other was snap-frozen for molecular analyses. At all different postnatal day (PND) time points (days 0, 5, 15, and 21), the whole litter was collected from each pregnancy and genotyped. Transcriptomics was done using kidney cortex from each time point for all genotypes.