Comprehensive phenotypic assessment of nonsense mutations in mitochondrial ND5 in mice.

IF 9.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Experimental and Molecular Medicine Pub Date : 2024-11-01 DOI:10.1038/s12276-024-01333-9
Sanghun Kim, Seul Gi Park, Jieun Kim, Seongho Hong, Sang-Mi Cho, Soo-Yeon Lim, Eun-Kyoung Kim, Sungjin Ju, Su Bin Lee, Sol Pin Kim, Tae Young Jeong, Yeji Oh, Seunghun Han, Hae-Rim Kim, Taek Chang Lee, Hyoung-Chin Kim, Won Kee Yoon, Tae Hyeon An, Kyoung-Jin Oh, Ki-Hoan Nam, Seonghyun Lee, Kyoungmi Kim, Je Kyung Seong, Hyunji Lee
{"title":"Comprehensive phenotypic assessment of nonsense mutations in mitochondrial ND5 in mice.","authors":"Sanghun Kim, Seul Gi Park, Jieun Kim, Seongho Hong, Sang-Mi Cho, Soo-Yeon Lim, Eun-Kyoung Kim, Sungjin Ju, Su Bin Lee, Sol Pin Kim, Tae Young Jeong, Yeji Oh, Seunghun Han, Hae-Rim Kim, Taek Chang Lee, Hyoung-Chin Kim, Won Kee Yoon, Tae Hyeon An, Kyoung-Jin Oh, Ki-Hoan Nam, Seonghyun Lee, Kyoungmi Kim, Je Kyung Seong, Hyunji Lee","doi":"10.1038/s12276-024-01333-9","DOIUrl":null,"url":null,"abstract":"<p><p>Mitochondrial dysfunction induced by mitochondrial DNA (mtDNA) mutations has been implicated in various human diseases. A comprehensive analysis of mitochondrial genetic disorders requires suitable animal models for human disease studies. While gene knockout via premature stop codons is a powerful method for investigating the unique functions of target genes, achieving knockout of mtDNA has been rare. Here, we report the genotypes and phenotypes of heteroplasmic MT-ND5 gene-knockout mice. These mutant mice presented damaged mitochondrial cristae in the cerebral cortex, hippocampal atrophy, and asymmetry, leading to learning and memory abnormalities. Moreover, mutant mice are susceptible to obesity and thermogenetic disorders. We propose that these mtDNA gene-knockdown mice could serve as valuable animal models for studying the MT-ND5 gene and developing therapies for human mitochondrial disorders in the future.</p>","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental and Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s12276-024-01333-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Mitochondrial dysfunction induced by mitochondrial DNA (mtDNA) mutations has been implicated in various human diseases. A comprehensive analysis of mitochondrial genetic disorders requires suitable animal models for human disease studies. While gene knockout via premature stop codons is a powerful method for investigating the unique functions of target genes, achieving knockout of mtDNA has been rare. Here, we report the genotypes and phenotypes of heteroplasmic MT-ND5 gene-knockout mice. These mutant mice presented damaged mitochondrial cristae in the cerebral cortex, hippocampal atrophy, and asymmetry, leading to learning and memory abnormalities. Moreover, mutant mice are susceptible to obesity and thermogenetic disorders. We propose that these mtDNA gene-knockdown mice could serve as valuable animal models for studying the MT-ND5 gene and developing therapies for human mitochondrial disorders in the future.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
小鼠线粒体 ND5 无义突变的综合表型评估。
线粒体 DNA(mtDNA)突变引起的线粒体功能障碍与多种人类疾病有关。要对线粒体遗传疾病进行全面分析,就必须为人类疾病研究建立合适的动物模型。虽然通过过早终止密码子敲除基因是研究目标基因独特功能的有效方法,但实现 mtDNA 基因敲除的方法还很少见。在这里,我们报告了异质MT-ND5基因敲除小鼠的基因型和表型。这些突变小鼠大脑皮层线粒体嵴受损、海马萎缩和不对称,导致学习和记忆异常。此外,突变小鼠易患肥胖症和发热性疾病。我们认为,这些 mtDNA 基因敲除小鼠可作为研究 MT-ND5 基因和开发人类线粒体疾病疗法的宝贵动物模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Experimental and Molecular Medicine
Experimental and Molecular Medicine 医学-生化与分子生物学
CiteScore
19.50
自引率
0.80%
发文量
166
审稿时长
3 months
期刊介绍: Experimental & Molecular Medicine (EMM) stands as Korea's pioneering biochemistry journal, established in 1964 and rejuvenated in 1996 as an Open Access, fully peer-reviewed international journal. Dedicated to advancing translational research and showcasing recent breakthroughs in the biomedical realm, EMM invites submissions encompassing genetic, molecular, and cellular studies of human physiology and diseases. Emphasizing the correlation between experimental and translational research and enhanced clinical benefits, the journal actively encourages contributions employing specific molecular tools. Welcoming studies that bridge basic discoveries with clinical relevance, alongside articles demonstrating clear in vivo significance and novelty, Experimental & Molecular Medicine proudly serves as an open-access, online-only repository of cutting-edge medical research.
期刊最新文献
Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL). Comprehensive phenotypic assessment of nonsense mutations in mitochondrial ND5 in mice. GLP-1 and its derived peptides mediate pain relief through direct TRPV1 inhibition without affecting thermoregulation. Interplay between membranes and biomolecular condensates in the regulation of membrane-associated cellular processes. Longitudinal analysis of genetic and epigenetic changes in human pluripotent stem cells in the landscape of culture-induced abnormality.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1