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Female rabbits have been successfully cloned from cumulus cells and the somatic cell nuclear transfer (SCNT) technology is well established. The present study generated hypoxanthine phosphoribosyltransferase (<jats:italic>HPRT<\/jats:italic>) gene knockout rabbits using recombinant adeno-associated virus-mediated homologous recombination and SCNT. Gene trap strategies were employed to enhance the gene targeting rates. The male and female gene knockout fibroblast cell lines were derived by different strategies. When male <jats:italic>HPRT<\/jats:italic> knockout cells were used for SCNT, no live rabbits were obtained. However, when female <jats:italic>HPRT<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> cells were used for SCNT, live, healthy rabbits were generated. The cloned <jats:italic>HPRT<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> rabbits were fertile at maturity. We demonstrate a new technique to produce gene-targeted rabbits. This approach may also be used in the genetic manipulation of different genes or in other species.<\/jats:p>","DOI":"10.1038\/srep16023","type":"journal-article","created":{"date-parts":[[2015,11,2]],"date-time":"2015-11-02T11:10:48Z","timestamp":1446462648000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Generation of hypoxanthine phosphoribosyltransferase gene knockout rabbits by homologous recombination and gene trapping through somatic cell nuclear transfer"],"prefix":"10.1038","volume":"5","author":[{"given":"Mingru","family":"Yin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenfu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengcheng","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengying","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,11,2]]},"reference":[{"key":"BFsrep16023_CR1","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/326292a0","volume":"326","author":"M Hooper","year":"1987","unstructured":"Hooper, M., Hardy, K., Handyside, A., Hunter, S. & Monk, M. 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