論文 - 詳細
| RRC ID | 88562 |
|---|---|
| 著者 | Terada K, Watanabe T, Yasuno N, Ohtsubo T, Shibata S, Ichida K, Hosoyamada M. |
| タイトル | Pseudogenization of the Slc23a4 gene is necessary for the survival of Xdh-deficient mice. |
| ジャーナル | Sci Rep |
| Abstract |
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. |
| 巻・号 | 15(1) |
| ページ | 3250 |
| 公開日 | 2025-1-25 |
| DOI | 10.1038/s41598-025-87751-9 |
| PII | 10.1038/s41598-025-87751-9 |
| PMID | 39863758 |
| PMC | PMC11762782 |
| MeSH | Animals Female Humans Hypoxanthine / urine Hypoxanthine Phosphoribosyltransferase / genetics Hypoxanthine Phosphoribosyltransferase / metabolism Longevity / genetics Male Mice Mice, Knockout Nucleobase Transport Proteins* / genetics Pseudogenes* / genetics Xanthine / urine Xanthine Dehydrogenase* / deficiency Xanthine Dehydrogenase* / genetics |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | 049682-UCD |