Scholarlink

<p>In most patients with type 1 xanthinuria caused by mutations in the xanthine dehydrogenase gene (<i>XDH</i>), no clinical complications, except for urinary stones, are observed. In contrast, all <i>Xdh</i>(− / −) mice die due to renal failure before reaching adulthood at 8&#xa0;weeks of age. Hypoxanthine or xanthine levels become excessive and thus toxic in <i>Xdh</i>(− / −) 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 (<i>Slc23a4</i>), which is a pseudogene in humans. <i>Hprt</i>(high)<i>Xdh</i>(− / −)<i>Slc23a4</i>(− / −) 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 <i>Hprt</i>(high)<i>Xdh</i>(− / −)<i>Slc23a4</i>(− / −) mice was lower than that of patients with type 1 xanthinuria. <i>Hprt</i>(high)<i>Xdh</i>(− / −)<i>Slc23a4</i>(− / −) mice exhibited renal impairment, accompanied by high plasma creatinine levels and anemia. Moreover, female <i>Hprt</i>(high)<i>Xdh</i>(− / −)<i>Slc23a4</i>(− / −) mice produced offspring that did not survive. In conclusion, for the first time, we established that <i>Xdh</i>(− / −) mice survive to adulthood.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pseudogenization of the Slc23a4 gene is necessary for the survival of Xdh-deficient mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月25日

查看全文
  • Kazuki Terada,
  • Tamaki Watanabe,
  • Nobuhiro Yasuno,
  • Toshio Ohtsubo,
  • Shigeru Shibata,
  • Kimiyoshi Ichida,
  • Makoto Hosoyamada

摘要

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.