ID 112917
タイトル別表記
TP53-mutant pigs generated by zygote electroporation
著者
Nguyen, Nhien Thi Tokushima University
Le, Quynh Anh Tokushima University
Hirano, Takayuki Tokushima University
Nakai, Michiko National Agriculture and Food Research Organization (NARO)
Fuchimoto, Dai-ichiro National Agriculture and Food Research Organization (NARO)
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
PLOS ONE
ISSN
19326203
出版者
PLOS
13
10
開始ページ
e0206360
発行日
2018-10-23
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.
EDB ID
347033
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
生物資源系
先端酵素学研究所