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A novel tissue specific alternative splicing variant mitigates phenotypes in Ets2 frame-shift mutant models
http://hdl.handle.net/10061/14274
http://hdl.handle.net/10061/142743ce204df-0d63-478c-b3ea-228ac2f4135e
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-05-27 | |||||
タイトル | ||||||
タイトル | A novel tissue specific alternative splicing variant mitigates phenotypes in Ets2 frame-shift mutant models | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Biological models | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Biological techniques | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Developmental biology | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Gene expression analysis | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Genetics | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Mutation | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | RNA splicing | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Kishimoto, Yuki
× Kishimoto, Yuki× Nishiura, Iori× Hirata, Wataru× Yuri, Shunsuke× Yamamoto, Nami× Ikawa, Masahito× Isotani, Ayako |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | E26 avian leukemia oncogene 2, 3′ domain (Ets2) has been implicated in various biological processes. An Ets2 mutant model (Ets2db1/db1), which lacks the DNA-binding domain, was previously reported to exhibit embryonic lethality caused by a trophoblast abnormality. This phenotype could be rescued by tetraploid complementation, resulting in pups with wavy hair and curly whiskers. Here, we generated new Ets2 mutant models with a frame-shift mutation in exon 8 using the CRISPR/Cas9 method. Homozygous mutants could not be obtained by natural mating as embryonic development stopped before E8.5, as previously reported. When we rescued them by tetraploid complementation, these mice did not exhibit wavy hair or curly whisker phenotypes. Our newly generated mice exhibited exon 8 skipping, which led to in-frame mutant mRNA expression in the skin and thymus but not in E7.5 Ets2em1/em1 embryos. This exon 8-skipped Ets2 mRNA was translated into protein, suggesting that this Ets2 mutant protein complemented the Ets2 function in the skin. Our data implies that novel splicing variants incidentally generated after genome editing may complicate the phenotypic analysis but may also give insight into the new mechanisms related to biological gene functions. | |||||
言語 | en | |||||
書誌情報 |
en : Scientific Reports 巻 11, 発行日 2021-04-15 |
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artnum | ||||||
値 | 8297 | |||||
出版者 | ||||||
出版者 | Nature Research | |||||
言語 | en | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2045-2322 | |||||
PubMed番号 | ||||||
関連タイプ | isReplacedBy | |||||
識別子タイプ | PMID | |||||
関連識別子 | 33859300 | |||||
出版者版DOI | ||||||
関連タイプ | isReplacedBy | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1038/s41598-021-87751-5 | |||||
出版者版URI | ||||||
関連タイプ | isReplacedBy | |||||
識別子タイプ | URI | |||||
関連識別子 | https://www.nature.com/articles/s41598-021-87751-5 | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | c The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. |