| First Author | Terada K | Year | 2025 |
| Journal | Sci Rep | Volume | 15 |
| Issue | 1 | Pages | 3250 |
| PubMed ID | 39863758 | Mgi Jnum | J:361518 |
| Mgi Id | MGI:7858482 | Doi | 10.1038/s41598-025-87751-9 |
| Citation | Terada K, et al. (2025) Pseudogenization of the Slc23a4 gene is necessary for the survival of Xdh-deficient mice. Sci Rep 15(1):3250 |
| abstractText | In most patients with type 1 xanthinuria caused by mutations in the xanthine dehydrogenase gene (XDH), no clinical complications, except for urinary stones, are observed. In contrast, all Xdh(- / -) mice die due to renal failure before reaching adulthood at 8 weeks of age. Hypoxanthine or xanthine levels become excessive and thus toxic in Xdh(- / -) mice because enhancing the activity of hypoxanthine phosphoribosyl transferase (HPRT), which is an enzyme that uses hypoxanthine as a substrate, slightly increases the life span of these mice. In this study, we targeted the mouse intestinal sodium-dependent nucleobase transporter (SNBT) gene (Slc23a4), which is a pseudogene in humans. Hprt(high)Xdh(- / -)Slc23a4(- / -) mice had a longer life span and reached adulthood. The urinary xanthine excretion of these mice was 20-fold greater than that of patients with type 1 xanthinuria. The urinary hypoxanthine/xanthine ratio of Hprt(high)Xdh(- / -)Slc23a4(- / -) mice was lower than that of patients with type 1 xanthinuria. Hprt(high)Xdh(- / -)Slc23a4(- / -) mice exhibited renal impairment, accompanied by high plasma creatinine levels and anemia. Moreover, female Hprt(high)Xdh(- / -)Slc23a4(- / -) mice produced offspring that did not survive. In conclusion, for the first time, we established that Xdh(- / -) mice survive to adulthood. |
