• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Slc23a4基因的假基因化对于缺乏Xdh的小鼠的存活是必要的。

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

作者信息

Terada Kazuki, Watanabe Tamaki, Yasuno Nobuhiro, Ohtsubo Toshio, Shibata Shigeru, Ichida Kimiyoshi, Hosoyamada Makoto

机构信息

Laboratory of Human Physiology and Pathology, Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan.

Laboratory of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan.

出版信息

Sci Rep. 2025 Jan 25;15(1):3250. doi: 10.1038/s41598-025-87751-9.

DOI:10.1038/s41598-025-87751-9
PMID:39863758
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11762782/
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.

摘要

在大多数由黄嘌呤脱氢酶基因（XDH）突变引起的1型黄嘌呤尿症患者中，除了尿路结石外，未观察到临床并发症。相比之下，所有Xdh(- / -)小鼠在8周龄成年前因肾衰竭而死亡。在Xdh(- / -)小鼠中，次黄嘌呤或黄嘌呤水平会变得过高并因此产生毒性，因为增强次黄嘌呤磷酸核糖转移酶（HPRT）的活性（HPRT是一种以次黄嘌呤为底物的酶）会略微延长这些小鼠的寿命。在本研究中，我们针对小鼠肠道钠依赖性核碱基转运体（SNBT）基因（Slc23a4），该基因在人类中是一个假基因。Hprt(high)Xdh(- / -)Slc23a4(- / -)小鼠寿命更长并能成年。这些小鼠的尿黄嘌呤排泄量比1型黄嘌呤尿症患者高20倍。Hprt(high)Xdh(- / -)Slc23a4(- / -)小鼠的尿次黄嘌呤/黄嘌呤比值低于1型黄嘌呤尿症患者。Hprt(high)Xdh(- / -)Slc23a4(- / -)小鼠表现出肾功能损害，伴有高血浆肌酐水平和贫血。此外，雌性Hprt(high)Xdh(- / -)Slc23a4(- / -)小鼠产下的后代无法存活。总之，我们首次证实Xdh(- / -)小鼠能存活至成年。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d6/11762782/55ca90f3be5c/41598_2025_87751_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d6/11762782/ae891cce9e40/41598_2025_87751_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d6/11762782/623d38fb0cae/41598_2025_87751_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d6/11762782/1b56daacd47e/41598_2025_87751_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d6/11762782/55ca90f3be5c/41598_2025_87751_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d6/11762782/ae891cce9e40/41598_2025_87751_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d6/11762782/623d38fb0cae/41598_2025_87751_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d6/11762782/1b56daacd47e/41598_2025_87751_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87d6/11762782/55ca90f3be5c/41598_2025_87751_Fig4_HTML.jpg

相似文献

1
Pseudogenization of the Slc23a4 gene is necessary for the survival of Xdh-deficient mice.Slc23a4基因的假基因化对于缺乏Xdh的小鼠的存活是必要的。
Sci Rep. 2025 Jan 25;15(1):3250. doi: 10.1038/s41598-025-87751-9.
2
Xanthine oxidoreductase knockout mice with high HPRT activity were not rescued by NAD replenishment.黄嘌呤氧化还原酶敲除小鼠的高 HPRT 活性不能通过 NAD 补充得到挽救。
Nucleosides Nucleotides Nucleic Acids. 2020;39(10-12):1465-1473. doi: 10.1080/15257770.2020.1725044. Epub 2020 Mar 4.
3
Aural toilet (ear cleaning) for chronic suppurative otitis media.慢性化脓性中耳炎的耳道清理（耳部清洁）
Cochrane Database Syst Rev. 2025 Jun 9;6(6):CD013057. doi: 10.1002/14651858.CD013057.pub3.
4
Pelvic floor muscle training with feedback or biofeedback for urinary incontinence in women.针对女性尿失禁的盆底肌训练及反馈或生物反馈训练
Cochrane Database Syst Rev. 2025 Mar 11;3(3):CD009252. doi: 10.1002/14651858.CD009252.pub2.
5
Perfecting a high hypoxanthine phosphoribosyltransferase activity-uricase KO mice to test the effects of purine- and non-purine-type xanthine dehydrogenase (XDH) inhibitors.完善高次黄嘌呤磷酸核糖基转移酶活性-尿酸氧化酶基因敲除小鼠，以测试嘌呤型和非嘌呤型黄嘌呤脱氢酶（XDH）抑制剂的效果。
Br J Pharmacol. 2020 May;177(10):2274-2285. doi: 10.1111/bph.14978. Epub 2020 Feb 18.
6
Prenatal administration of progestogens for preventing spontaneous preterm birth in women with a multiple pregnancy.孕激素产前给药预防多胎妊娠妇女自发性早产。
Cochrane Database Syst Rev. 2019 Nov 20;2019(11):CD012024. doi: 10.1002/14651858.CD012024.pub3.
7
Interventions for fertility preservation in women with cancer undergoing chemotherapy.对接受化疗的癌症女性进行生育力保存的干预措施。
Cochrane Database Syst Rev. 2025 Jun 19;6:CD012891. doi: 10.1002/14651858.CD012891.pub2.
8
Surveillance for Violent Deaths - National Violent Death Reporting System, 50 States, the District of Columbia, and Puerto Rico, 2022.暴力死亡监测——2022年全国暴力死亡报告系统，50个州、哥伦比亚特区和波多黎各
MMWR Surveill Summ. 2025 Jun 12;74(5):1-42. doi: 10.15585/mmwr.ss7405a1.
9
Absorbent products for moderate-heavy urinary and/or faecal incontinence in women and men.适用于女性和男性中重度尿失禁和/或大便失禁的吸收性产品。
Cochrane Database Syst Rev. 2008 Oct 8(4):CD007408. doi: 10.1002/14651858.CD007408.
10
Molecular feature-based classification of retroperitoneal liposarcoma: a prospective cohort study.基于分子特征的腹膜后脂肪肉瘤分类：一项前瞻性队列研究。
Elife. 2025 May 23;14:RP100887. doi: 10.7554/eLife.100887.

本文引用的文献

1
Hypouricaemia in a patient with hereditary xanthinuria type I.一名患有I型遗传性黄嘌呤尿症患者的低尿酸血症
Lancet. 2024 Apr 13;403(10435):1493. doi: 10.1016/S0140-6736(24)00472-0.
2
Adenine-induced animal model of chronic kidney disease: current applications and future perspectives.腺嘌呤诱导的慢性肾脏病动物模型：当前应用及未来展望。
Ren Fail. 2024 Dec;46(1):2336128. doi: 10.1080/0886022X.2024.2336128. Epub 2024 Apr 4.
3
Kidney Failure Secondary to Hereditary Xanthinuria due to a Homozygous Deletion of the XDH Gene in the Absence of Overt Kidney Stone Disease.
遗传性黄嘌呤尿症导致的肾脏衰竭，该疾病是由于 XDH 基因纯合缺失所致，且无明显肾脏结石病。
Nephron. 2024;148(8):578-583. doi: 10.1159/000536248. Epub 2024 Mar 25.
4
Deletion of Induces Xanthinuria with Obstructive Nephropathy and Major Metabolic Disorders in Mice.缺失导致小鼠黄嘌呤尿伴梗阻性肾病和主要代谢紊乱。
Kidney360. 2021 Sep 17;2(11):1793-1806. doi: 10.34067/KID.0001732021. eCollection 2021 Nov 25.
5
Hypothetical Mechanism of Exercise-Induced Acute Kidney Injury Associated with Renal Hypouricemia.运动诱导的急性肾损伤与肾性低尿酸血症相关的假说机制。
Biomedicines. 2021 Dec 6;9(12):1847. doi: 10.3390/biomedicines9121847.
6
Xanthine Oxidoreductase Inhibitors Suppress the Onset of Exercise-Induced AKI in High HPRT Activity - Double Knockout Mice.黄嘌呤氧化酶抑制剂可抑制高 HPRT 活性 - 双重敲除小鼠运动诱导的 AKI 的发生。
J Am Soc Nephrol. 2022 Feb;33(2):326-341. doi: 10.1681/ASN.2021050616. Epub 2021 Nov 19.
7
Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects.九个以色列家庭及两例德国散发病例中的经典型黄嘌呤尿症：分子、生化及群体遗传学方面
Biomedicines. 2021 Jul 7;9(7):788. doi: 10.3390/biomedicines9070788.
8
Effects of Allopurinol on the Progression of Chronic Kidney Disease.别嘌醇对慢性肾脏病进展的影响。
N Engl J Med. 2020 Jun 25;382(26):2504-2513. doi: 10.1056/NEJMoa1915833.
9
Xanthine oxidoreductase knockout mice with high HPRT activity were not rescued by NAD replenishment.黄嘌呤氧化还原酶敲除小鼠的高 HPRT 活性不能通过 NAD 补充得到挽救。
Nucleosides Nucleotides Nucleic Acids. 2020;39(10-12):1465-1473. doi: 10.1080/15257770.2020.1725044. Epub 2020 Mar 4.
10
A novel mutation in xanthine dehydrogenase in a case with xanthinuria in Hunan province of China.中国湖南省一例黄嘌呤尿症患者中黄嘌呤脱氢酶的一种新突变。
Clin Chim Acta. 2020 May;504:168-171. doi: 10.1016/j.cca.2020.02.012. Epub 2020 Feb 15.