論文

国際誌
2020年4月

Generation of viable PDX1 gene-edited founder pigs as providers of nonmosaics.

Molecular reproduction and development
  • Fuminori Tanihara
  • ,
  • Maki Hirata
  • ,
  • Nhien Thi Nguyen
  • ,
  • Quynh Anh Le
  • ,
  • Takayuki Hirano
  • ,
  • Takeshige Otoi

87
4
開始ページ
471
終了ページ
481
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/mrd.23335

Pancreatic duodenal homeobox 1 (PDX1) is a crucial gene for pancreas development during the fetal period. PDX1-modified pigs have the potential to be used as a model of diabetes mellitus. However, the severe health problems caused by the PDX1 mutation limit phenotypic studies of PDX1-modified pigs as diabetes models. In this study, we generated PDX1-modified pigs by the CRISPR/Cas9 system introduced into zygotes via electroporation and investigated the mosaicism, phenotypes, and inheritance of the resulting pigs. After the embryo transfer of PDX1-modified zygotes, nine mutant piglets were delivered. Two piglets were apancreatic biallelic mutants. For the other seven piglets, the ratio of mutant alleles to total alleles was 17.5-79.7%. Two mutant piglets with high mutation rates (67.7% and 79.7%) exhibited hypoplasia of the pancreas, whereas the other five piglets were healthy. One of the male mutant piglets was further analyzed. The ejaculated semen from the pig contained PDX1-mutant spermatozoa and the pig showed normal reproductive ability. In conclusion, the frequency of the PDX1 mutation is presumed to relate to pancreas formation, and PDX1 mutant founder pigs generated from zygotes introduced to the CRISPR/Cas9 system can serve as providers of nonmosaics to contribute to medical research on diabetes mellitus.

リンク情報
DOI
https://doi.org/10.1002/mrd.23335
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32166879
ID情報
  • DOI : 10.1002/mrd.23335
  • PubMed ID : 32166879

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