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Finding of a highly efficient ZFN pair for Aqpep gene functioning in murine zygotes

The generation efficiencies of mutation-induced mice when using engineered zinc-finger nucleases (ZFNs) have been generally 10 to 20% of obtained pups in previous studies. The discovery of high-affinity DNA-binding modules can contribute to the generation of various kinds of novel artificial chromat...

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Detalles Bibliográficos
Autores principales: FUJII, Wataru, ONUMA, Asuka, YOSHIOKA, Shin, NAGASHIMA, Keisuke, SUGIURA, Koji, NAITO, Kunihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Society for Reproduction and Development 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685226/
https://www.ncbi.nlm.nih.gov/pubmed/26460691
http://dx.doi.org/10.1262/jrd.2015-087
Descripción
Sumario:The generation efficiencies of mutation-induced mice when using engineered zinc-finger nucleases (ZFNs) have been generally 10 to 20% of obtained pups in previous studies. The discovery of high-affinity DNA-binding modules can contribute to the generation of various kinds of novel artificial chromatin-targeting tools, such as zinc-finger acetyltransferases, zinc-finger histone kinases and so on, as well as improvement of reported zinc-finger recombinases and zinc-finger methyltransferases. Here, we report a novel ZFN pair that has a highly efficient mutation-induction ability in murine zygotes. The ZFN pair induced mutations in all obtained mice in the target locus, exon 17 of aminopeptidase Q gene, and almost all of the pups had biallelic mutations. This high efficiency was also shown in the plasmid DNA transfected in a cultured human cell line. The induced mutations were inherited normally in the next generation. The zinc-finger modules of this ZFN pair are expected to contribute to the development of novel ZF-attached chromatin-targeting tools.