論文 - 詳細
| RRC ID | 58843 |
|---|---|
| 著者 | Horii T, Morita S, Hino S, Kimura M, Hino Y, Kogo H, Nakao M, Hatada I. |
| タイトル | Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome. |
| ジャーナル | Genome Biol |
| Abstract |
BACKGROUND:Epigenetic modifications, including DNA methylation, play an important role in gene silencing and genome stability. Consequently, epigenetic dysregulation can cause several diseases, such as cancer, obesity, diabetes, autism, and imprinting disorders. RESULTS:We validate three methods for the generation of epigenome-edited mice using the dCas9-SunTag and single-chain variable fragment-TET1 catalytic domain. We generate model mice for Silver-Russell syndrome (SRS), an imprinting disorder, by target-specific DNA demethylation in the H19 differentially methylated region. Like SRS patients, these mice show H19 upregulation and Igf2 downregulation, leading to severe intrauterine and postnatal growth retardation. CONCLUSION:This is the first report of an imprinting disease model animal generated by targeted demethylation of specific loci of the epigenome in fertilized eggs. Epigenome-edited animals are also useful for exploring the causative epimutations in epigenetic diseases. |
| 巻・号 | 21(1) |
| ページ | 77 |
| 公開日 | 2020-4-1 |
| DOI | 10.1186/s13059-020-01991-8 |
| PII | 10.1186/s13059-020-01991-8 |
| PMID | 32234052 |
| PMC | PMC7110793 |
| MeSH | Animals CRISPR-Cas Systems DNA Methylation Disease Models, Animal* Embryonic Stem Cells / metabolism Epigenesis, Genetic* Epigenome* Epigenomics / methods Humans Mice* RNA, Long Noncoding / genetics Silver-Russell Syndrome / diagnostic imaging Silver-Russell Syndrome / genetics* Zygote / metabolism |
| IF | 10.806 |
| 引用数 | 1 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |