ArticleEpigenetics & chromatin2022
Efficient generation of epigenetic disease model mice by epigenome editing using the piggyBac transposon system.
Article in Epigenetics & chromatin, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Highly efficient and low-mosaicismiScience · 2026Article
- Efficient generation of single-copy transgenic mice using piggyBat transposase from the little brown bat Myotis lucifugus†.Biology of reproduction · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- H19 and IGF2 imprinting from embryogenesis to oncogenesis.Frontiers in cell and developmental biology · 2026Review
- DNA methylation shapes the Polycomb landscape during the exit from naive pluripotency.Nature structural & molecular biology · 2025Article
- The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation.Nucleic acids research · 2024Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEpigenome-edited animal models enable direct demonstration of disease causing epigenetic mutations. Transgenic (TG) mice stably expressing epigenome-editing factors exhibit dramatic and stable changes in target epigenome modifications. Successful germline transmission of a transgene from founder mice to offspring will yield a sufficient number of epigenome-edited mice for phenotypic analysis; however, if the epigenetic mutation has a detrimental phenotypic effect, it can become difficult to obtain the next generation of animals. In this case, the phenotype of founder mice must be analyzed directly. Unfortunately, current TG mouse production efficiency (TG founders per pups born) is relatively low, and improvements would increase the versatility of this technology.
resultsIn the current study, we describe an approach to generate epigenome-edited TG mice using a combination of both the dCas9-SunTag and piggyBac (PB) transposon systems. Using this system, we successfully generated mice with demethylation of the differential methylated region of the H19 gene (H19-DMR), as a model for Silver-Russell syndrome (SRS). SRS is a disorder leading to growth retardation, resulting from low insulin-like growth factor 2 (IGF2) gene expression, often caused by epimutations at the H19-IGF2 locus. Under optimized conditions, the efficiency of TG mice production using the PB system was approximately threefold higher than that using the conventional method. TG mice generated by this system showed demethylation of the targeted DNA region and associated changes in gene expression. In addition, these mice exhibited some features of SRS, including intrauterine and postnatal growth retardation, due to demethylation of H19-DMR.
conclusionsThe dCas9-SunTag and PB systems serve as a simple and reliable platform for conducting direct experiments using epigenome-edited founder mice.
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