{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T20:05:36Z","timestamp":1762459536837},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:00:00Z","timestamp":1512432000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:00:00Z","timestamp":1512432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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<jats:sup>+\/\u2212<\/jats:sup> cloned pigs died of severe bleeding at an early age, as was the case for male F8<jats:sup>\u2212\/Y<\/jats:sup> cloned pigs, thus making it impossible to obtain progeny. In this study, therefore, we produced sperm from F8<jats:sup>\u2212\/Y<\/jats:sup> cloned pigs by grafting their foetal testicular tissue into nude mice. Two F8<jats:sup>+\/\u2212<\/jats:sup> female pigs were generated from oocytes injected with xenogeneic sperm. Unlike the F8<jats:sup>+\/\u2212<\/jats:sup> cloned pigs, they remained asymptomatic, and delivered five F8<jats:sup>\u2212\/Y<\/jats:sup> and four F8<jats:sup>+\/\u2212<\/jats:sup> pigs after being crossed with wild-type boars. The descendant F8<jats:sup>\u2212\/Y<\/jats:sup> pigs conserved the haemophilia phenotype. Thus, the present F8<jats:sup>+\/\u2212<\/jats:sup> pigs show resolution of the phenotypic abnormality, and will facilitate production of F8<jats:sup>\u2212\/Y<\/jats:sup> 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.<\/jats:p>","DOI":"10.1038\/s41598-017-17017-6","type":"journal-article","created":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T15:56:37Z","timestamp":1511970997000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Establishment of a strain of haemophilia-A pigs by xenografting of foetal testicular tissue from neonatally moribund cloned pigs"],"prefix":"10.1038","volume":"7","author":[{"given":"Hiroyuki","family":"Kaneko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiko","family":"Nakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiichiro","family":"Fuchimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunichi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoichiro","family":"Sembon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Noguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Onishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,12,5]]},"reference":[{"key":"17017_CR1","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/nature00918","volume":"418","author":"A Honaramooz","year":"2002","unstructured":"Honaramooz, A. et al. 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