| Item type |
文献 / Documents(1) |
| 公開日 |
2019-01-11 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 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 |
| 出版社版DOI |
|
|
|
関連識別子 |
https://doi.org/10.1371/journal.pone.0206360 |
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|
関連名称 |
10.1371/journal.pone.0206360 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Generation of a TP53-modified porcine cancer model by CRISPR/Cas9-mediated gene modification in porcine zygotes via electroporation |
| タイトル別表記 |
|
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その他のタイトル |
TP53-mutant pigs generated by zygote electroporation |
| 著者 |
谷原, 史倫
平田, 真樹
Nguyen, Nhien Thi
Le, Quynh Anh
ヒラノ, タカユキ
竹本, 龍也
ナカイ, ミチコ
フチモト, ダイイチロウ
音井, 威重
|
| 抄録 |
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|
内容記述 |
TP53 (which encodes p53) is one of the most frequently mutated genes in cancers. In this study, we generated TP53-mutant pigs by gene editing via electroporation of the Cas9 protein (GEEP), a process that involves introducing the Cas9 protein and single-guide RNA (sgRNA) targeting exon 3 and intron 4 of TP53 into in vitro-fertilized zygotes. Zygotes modified by the sgRNAs were transferred to recipients, two of which gave birth to a total of 11 piglets. Of those 11 piglets, 9 survived. Molecular genetic analysis confirmed that 6 of 9 live piglets carried mutations in TP53, including 2 piglets with no wild-type (WT) sequences and 4 genetically mosaic piglets with WT sequences. One mosaic piglet had 142 and 151 bp deletions caused by a combination of the two sgRNAs. These piglets were continually monitored for 16 months and three of the genome-edited pigs (50%) exhibited various tumor phenotypes that we presumed were caused by TP53 mutations. Two mutant pigs with no WT sequences developed mandibular osteosarcoma and nephroblastoma. The mosaic pig with a deletion between targeting sites of two sgRNAs exhibited malignant fibrous histiocytoma. Tumor phenotypes of TP53 mosaic mutant pigs have not been previously reported. Our results indicated that the mutations caused by gene editing successfully induced tumor phenotypes in both TP53 mosaic- and bi-allelic mutant pigs. |
| 書誌情報 |
en : PLOS ONE
巻 13,
号 10,
p. e0206360,
発行日 2018-10-23
|
| 収録物ID |
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|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
19326203 |
| 出版者 |
|
|
出版者 |
PLOS |
| 権利情報 |
|
|
権利情報 |
© 2018 Tanihara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
|
|
識別子 |
347033 |
| 言語 |
|
|
言語 |
eng |
pone_10_13_e0206360.pdf (2.11 MB)
