• 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

缺乏 Alkbh1 的小鼠表现出性别比例扭曲和单侧眼睛缺陷。

Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects.

机构信息

Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital and University of Oslo, Oslo, Norway.

出版信息

PLoS One. 2010 Nov 3;5(11):e13827. doi: 10.1371/journal.pone.0013827.

DOI:10.1371/journal.pone.0013827
PMID:21072209
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2972218/
Abstract

BACKGROUND

Escherichia coli AlkB is a 2-oxoglutarate- and iron-dependent dioxygenase that reverses alkylated DNA damage by oxidative demethylation. Mouse AlkB homolog 1 (Alkbh1) is one of eight members of the newly discovered family of mammalian dioxygenases.

METHODS AND FINDINGS

In the present study we show non-Mendelian inheritance of the Alkbh1 targeted allele in mice. Both Alkbh1(-/-) and heterozygous Alkbh1(+/-) offspring are born at a greatly reduced frequency. Additionally, the sex-ratio is considerably skewed against female offspring, with one female born for every three to four males. Most mechanisms that cause segregation distortion, act in the male gametes and affect male fertility. The skewing of the sexes appears to be of paternal origin, and might be set in the pachythene stage of meiosis during spermatogenesis, in which Alkbh1 is upregulated more than 10-fold. In testes, apoptotic spermatids were revealed in 5-10% of the tubules in Alkbh1(-/-) adults. The deficiency of Alkbh1 also causes misexpression of Bmp2, 4 and 7 at E11.5 during embryonic development. This is consistent with the incompletely penetrant phenotypes observed, particularly recurrent unilateral eye defects and craniofacial malformations.

CONCLUSIONS

Genetic and phenotypic assessment suggests that Alkbh1 mediates gene regulation in spermatogenesis, and that Alkbh1 is essential for normal sex-ratio distribution and embryonic development in mice.

摘要

背景

大肠杆菌 AlkB 是一种依赖 2- 酮戊二酸和铁的双加氧酶，通过氧化脱甲基作用逆转烷基化的 DNA 损伤。小鼠 AlkB 同源物 1（Alkbh1）是新发现的哺乳动物双加氧酶家族的八个成员之一。

方法和发现

在本研究中，我们显示了小鼠中 Alkbh1 靶向等位基因的非孟德尔遗传。Alkbh1(-/-) 和杂合子 Alkbh1(+/-) 后代的出生率大大降低。此外，性别比例严重偏向雌性后代，每三到四个雄性后代中就有一个雌性后代。大多数导致分离失真的机制作用于雄性配子，并影响雄性生育能力。性别偏斜似乎来自父本，并且可能在精子发生的减数分裂粗线期发生，在此期间 Alkbh1 的上调超过 10 倍。在睾丸中，Alkbh1(-/-) 成年大鼠中 5-10%的小管中显示出凋亡的精母细胞。Alkbh1 的缺乏也导致 Bmp2、4 和 7 在胚胎发育过程中的 E11.5 表达错误。这与观察到的不完全外显率表型一致，特别是复发性单侧眼睛缺陷和颅面畸形。

结论

遗传和表型评估表明，Alkbh1 介导精子发生中的基因调控，并且 Alkbh1 对于正常的性别比例分布和小鼠胚胎发育是必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/bf59f88a1dba/pone.0013827.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/71c649d7b649/pone.0013827.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/85d89c064e04/pone.0013827.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/b3e0f4c46d99/pone.0013827.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/94ed687cb7f6/pone.0013827.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/4803545988df/pone.0013827.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/c0899ec0c3ac/pone.0013827.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/5bd35dd8af46/pone.0013827.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/bf59f88a1dba/pone.0013827.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/71c649d7b649/pone.0013827.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/85d89c064e04/pone.0013827.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/b3e0f4c46d99/pone.0013827.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/94ed687cb7f6/pone.0013827.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/4803545988df/pone.0013827.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/c0899ec0c3ac/pone.0013827.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/5bd35dd8af46/pone.0013827.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b9/2972218/bf59f88a1dba/pone.0013827.g008.jpg

相似文献

1
Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects.缺乏 Alkbh1 的小鼠表现出性别比例扭曲和单侧眼睛缺陷。
PLoS One. 2010 Nov 3;5(11):e13827. doi: 10.1371/journal.pone.0013827.
2
Impaired placental trophoblast lineage differentiation in Alkbh1(-/-) mice.Alkbh1基因敲除小鼠胎盘滋养层细胞系分化受损。
Dev Dyn. 2008 Feb;237(2):316-27. doi: 10.1002/dvdy.21418.
3
Role of ALKBH1 in the Core Transcriptional Network of Embryonic Stem Cells.ALKBH1在胚胎干细胞核心转录网络中的作用
Cell Physiol Biochem. 2016;38(1):173-84. doi: 10.1159/000438619. Epub 2016 Jan 15.
4
ALKBH1 is dispensable for abasic site cleavage during base excision repair and class switch recombination.ALKBH1 在碱基切除修复和类别转换重组过程中对于碱基损伤的切割并非必需。
PLoS One. 2013 Jun 25;8(6):e67403. doi: 10.1371/journal.pone.0067403. Print 2013.
5
ALKBH1 is a histone H2A dioxygenase involved in neural differentiation.ALKBH1 是一种组蛋白 H2A 双加氧酶，参与神经分化。
Stem Cells. 2012 Dec;30(12):2672-82. doi: 10.1002/stem.1228.
6
Characterization of human AlkB homolog 1 produced in mammalian cells and demonstration of mitochondrial dysfunction in ALKBH1-deficient cells.在哺乳动物细胞中产生的人类AlkB同源物1的特性鉴定以及ALKBH1缺陷细胞中线粒体功能障碍的证明。
Biochem Biophys Res Commun. 2018 Jan 1;495(1):98-103. doi: 10.1016/j.bbrc.2017.10.158. Epub 2017 Oct 31.
7
Alkbh1 and Tzfp repress a non-repeat piRNA cluster in pachytene spermatocytes.Alkbh1 和 Tzfp 抑制精母细胞中一个非重复的 piRNA 簇。
Nucleic Acids Res. 2012 Nov;40(21):10950-63. doi: 10.1093/nar/gks839. Epub 2012 Sep 10.
8
Biochemical Characterization of AP Lyase and mA Demethylase Activities of Human AlkB Homologue 1 (ALKBH1).人烷基化修复蛋白同源物1（ALKBH1）的AP裂解酶和mA去甲基酶活性的生化特性
Biochemistry. 2017 Apr 4;56(13):1899-1910. doi: 10.1021/acs.biochem.7b00060. Epub 2017 Mar 21.
9
A covalent protein-DNA 5'-product adduct is generated following AP lyase activity of human ALKBH1 (AlkB homologue 1).人 ALKBH1（AlkB 同源物 1）的 AP 裂合酶活性产生之后会生成共价的蛋白质-DNA 5′-产物加合物。
Biochem J. 2013 Jun 15;452(3):509-18. doi: 10.1042/BJ20121908.
10
Homology modeling, molecular dynamics, and site-directed mutagenesis study of AlkB human homolog 1 (ALKBH1).人AlkB同源蛋白1（ALKBH1）的同源性建模、分子动力学及定点诱变研究
J Mol Graph Model. 2014 Nov;54:123-30. doi: 10.1016/j.jmgm.2014.10.013. Epub 2014 Oct 27.

引用本文的文献

1
ALKBH1 drives tumorigenesis and drug resistance via tRNA decoding reprogramming and codon-biased translation.ALKBH1通过tRNA解码重编程和密码子偏向性翻译驱动肿瘤发生和耐药性。
Cancer Discov. 2025 Aug 4. doi: 10.1158/2159-8290.CD-24-1043.
2
ALKBH1: emerging biomarker and therapeutic target for cancer treatment.ALKBH1：癌症治疗中新兴的生物标志物和治疗靶点。
Discov Oncol. 2024 Dec 20;15(1):816. doi: 10.1007/s12672-024-01696-5.
3
Creation of true interspecies hybrids: Rescue of hybrid class with hybrid cytoplasm affecting growth and metabolism.

本文引用的文献

1
Signaling pathways in human skeletal dysplasias.人类骨骼发育不良症中的信号通路。
Annu Rev Genomics Hum Genet. 2010;11:189-217. doi: 10.1146/annurev-genom-082908-150158.
2
Divergent ß-hairpins determine double-strand versus single-strand substrate recognition of human AlkB-homologues 2 and 3.不同的β发夹结构决定了人源 AlkB 同源物 2 和 3 对双链和单链底物的识别。
Nucleic Acids Res. 2010 Oct;38(19):6447-55. doi: 10.1093/nar/gkq518. Epub 2010 Jun 4.
3
Bone morphogenetic protein 7 (BMP7) mutations are associated with variable ocular, brain, ear, palate, and skeletal anomalies.
真正的种间杂种的创造：拯救具有影响生长和代谢的杂种细胞质的杂种类。
Sci Adv. 2024 Oct 25;10(43):eadq4339. doi: 10.1126/sciadv.adq4339. Epub 2024 Oct 23.
4
Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family.来自AlkB样家族的真核生物α-酮戊二酸依赖性双加氧酶对大分子的脱烷基作用。
Curr Issues Mol Biol. 2024 Sep 20;46(9):10462-10491. doi: 10.3390/cimb46090622.
5
The biological function of demethylase ALKBH1 and its role in human diseases.去甲基化酶ALKBH1的生物学功能及其在人类疾病中的作用。
Heliyon. 2024 Jun 24;10(13):e33489. doi: 10.1016/j.heliyon.2024.e33489. eCollection 2024 Jul 15.
6
ALKBH1 promotes HIF-1α-mediated glycolysis by inhibiting N-glycosylation of LAMP2A.ALKBH1通过抑制LAMP2A的N-糖基化来促进HIF-1α介导的糖酵解。
Cell Mol Life Sci. 2024 Mar 12;81(1):130. doi: 10.1007/s00018-024-05152-z.
7
A DNA adenine demethylase impairs PRC2-mediated repression of genes marked by a specific chromatin signature.一种 DNA 腺嘌呤去甲基化酶可损害 PRC2 介导的特定染色质特征标记基因的抑制作用。
Genome Biol. 2023 Aug 30;24(1):198. doi: 10.1186/s13059-023-03042-4.
8
N6-methyladenine: A Rare and Dynamic DNA Mark.N6-甲基腺嘌呤：一种罕见且动态的DNA标记。
Adv Exp Med Biol. 2022;1389:177-210. doi: 10.1007/978-3-031-11454-0_8.
9
Effects of biological sex mismatch on neural progenitor cell transplantation for spinal cord injury in mice.生物性别错配对小鼠脊髓损伤神经祖细胞移植的影响。
Nat Commun. 2022 Sep 14;13(1):5380. doi: 10.1038/s41467-022-33134-x.
10
Ablation of the Cluster Causes a Skewed Sex Ratio in Mice.簇的消融导致小鼠出现偏性性别比。
Front Endocrinol (Lausanne). 2022 May 23;13:893854. doi: 10.3389/fendo.2022.893854. eCollection 2022.
骨形态发生蛋白 7（BMP7）突变与可变的眼部、脑部、耳部、腭裂和骨骼异常有关。
Hum Mutat. 2010 Jul;31(7):781-7. doi: 10.1002/humu.21280.
4
Crystal structure of the FTO protein reveals basis for its substrate specificity.FTO 蛋白的晶体结构揭示了其底物特异性的基础。
Nature. 2010 Apr 22;464(7292):1205-9. doi: 10.1038/nature08921. Epub 2010 Apr 7.
5
Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival.人源 AlkB 同源物 ABH8 是一种 tRNA 甲基转移酶，对于摆动尿嘧啶修饰和 DNA 损伤存活是必需的。
Mol Cell Biol. 2010 May;30(10):2449-59. doi: 10.1128/MCB.01604-09. Epub 2010 Mar 22.
6
Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding.哺乳动物的 ALKBH8 具有 tRNA 甲基转移酶活性，该酶对于多种与翻译解码相关的摆动尿嘧啶修饰的生物发生是必需的。
Mol Cell Biol. 2010 Apr;30(7):1814-27. doi: 10.1128/MCB.01602-09. Epub 2010 Feb 1.
7
Regulation of the osteoblast-specific transcription factor Osterix by NO66, a Jumonji family histone demethylase.NO66，一种组蛋白去甲基化酶 Jumonji 家族，调控成骨细胞特异性转录因子 Osterix。
EMBO J. 2010 Jan 6;29(1):68-79. doi: 10.1038/emboj.2009.332. Epub 2009 Nov 19.
8
Jmjd1a demethylase-regulated histone modification is essential for cAMP-response element modulator-regulated gene expression and spermatogenesis.Jmjd1a 去甲基化酶调控的组蛋白修饰对于 cAMP 反应元件调节剂调控的基因表达和精子发生至关重要。
J Biol Chem. 2010 Jan 22;285(4):2758-70. doi: 10.1074/jbc.M109.066845. Epub 2009 Nov 12.
9
Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations.编码双加氧酶的FTO基因功能丧失性突变会导致严重的生长发育迟缓及多种畸形。
Am J Hum Genet. 2009 Jul;85(1):106-11. doi: 10.1016/j.ajhg.2009.06.002. Epub 2009 Jun 25.
10
Bmp2 and Bmp4 genetically interact to support multiple aspects of mouse development including functional heart development.骨形态发生蛋白2（Bmp2）和骨形态发生蛋白4（Bmp4）在基因层面相互作用，以支持小鼠发育的多个方面，包括功能性心脏发育。
Genesis. 2009 Jun;47(6):374-84. doi: 10.1002/dvg.20511.