Genome Biology, 2020-04, Vol.21 (1), p.77-77, Article 77
2020
Details
- Autor(en) / Beteiligte
- Titel
- Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome
- Ist Teil von
- Genome Biology, 2020-04, Vol.21 (1), p.77-77, Article 77
- Ort / Verlag
- England: BioMed Central
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- SpringerLink (Online service)
- Beschreibungen/Notizen
- 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. 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1474-760X, 1474-7596eISSN: 1474-760XDOI: 10.1186/s13059-020-01991-8Titel-ID: cdi_doaj_primary_oai_doaj_org_article_ddbaf52b3f00427c813f81dfb8ab45b8
- Format
- –
- Schlagworte
- Animal models, Animals, Autism, Binding sites, CRISPR, CRISPR-Cas Systems, CRISPR/Cas9, dCas9, Demethylation, Deoxyribonucleic acid, Diabetes mellitus, Disease, Disease Models, Animal, DNA, DNA Methylation, Eggs, Embryonic Stem Cells - metabolism, Embryos, Epigenesis, Genetic, Epigenetics, Epigenome, Epigenome editing, Epigenomics - methods, Gene expression, Gene silencing, Genomes, Growth rate, Humans, Imprinting, Insulin-like growth factor II, Methods, Mice, Proteins, RNA, Long Noncoding - genetics, Silver-Russell syndrome, Silver-Russell Syndrome - diagnostic imaging, Silver-Russell Syndrome - genetics, Stem cells, Zygote - metabolism