論文

査読有り
2017年12月

Establishment of a strain of haemophilia-A pigs by xenografting of foetal testicular tissue from neonatally moribund cloned pigs

SCIENTIFIC REPORTS
  • Hiroyuki Kaneko
  • ,
  • Kazuhiro Kikuchi
  • ,
  • Michiko Nakai
  • ,
  • Daiichiro Fuchimoto
  • ,
  • Shunichi Suzuki
  • ,
  • Shoichiro Sembon
  • ,
  • Junko Noguchi
  • ,
  • Akira Onishi

7
1
開始ページ
17026
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-017-17017-6
出版者・発行元
NATURE PUBLISHING GROUP

Grafting of testicular tissue into immunodeficient mice makes it possible to obtain functional sperm from immature donor animals that cannot be used for reproduction. We have developed a porcine model of human haemophilia A (haemophilia-A pigs) by nuclear transfer cloning from foetal fibroblasts after disruption of the X-linked coagulation factor VIII (F8) gene. Despite having a recessive condition, female F8(+/-) cloned pigs died of severe bleeding at an early age, as was the case for male F8(-/Y) cloned pigs, thus making it impossible to obtain progeny. In this study, therefore, we produced sperm from F8(-/Y) cloned pigs by grafting their foetal testicular tissue into nude mice. Two F8(+/-) female pigs were generated from oocytes injected with xenogeneic sperm. Unlike the F8(+/-) cloned pigs, they remained asymptomatic, and delivered five F8(-/Y) and four F8(+/-) pigs after being crossed with wild-type boars. The descendant F8(-/Y) pigs conserved the haemophilia phenotype. Thus, the present F8(+/-) pigs show resolution of the phenotypic abnormality, and will facilitate production of F8(-/Y) pigs as founders of a strain of haemophilia-A pigs for the development of new therapeutics for haemophilia A. This strategy will be applicable to other genetically modified pigs.

リンク情報
DOI
https://doi.org/10.1038/s41598-017-17017-6
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29208927
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000417051000076&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/s41598-017-17017-6
  • ISSN : 2045-2322
  • PubMed ID : 29208927
  • Web of Science ID : WOS:000417051000076

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