{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:15:35Z","timestamp":1792592135514,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T00:00:00Z","timestamp":1586476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DE027046"],"award-info":[{"award-number":["DE027046"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011781","name":"Shriners Hospitals for Children","doi-asserted-by":"publisher","award":["85900"],"award-info":[{"award-number":["85900"]}],"id":[{"id":"10.13039\/100011781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Heterozygous deletion of <jats:italic>Six2<\/jats:italic>, which encodes a member of <jats:italic>sine oculis<\/jats:italic> homeobox family transcription factors, has recently been associated with the frontonasal dysplasia syndrome FND4. Previous studies showed that <jats:italic>Six2<\/jats:italic> is expressed in multiple tissues during craniofacial development in mice, including embryonic head mesoderm, postmigratory frontonasal neural crest cells, and epithelial and mesenchymal cells of the developing palate and nasal structures. Whereas <jats:italic>Six2<\/jats:italic><jats:sup>\n<jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice exhibited cranial base defects but did not recapitulate frontonasal phenotypes of FND4 patients, <jats:italic>Six1<\/jats:italic><jats:sup>\n<jats:italic>\u2212\/\u2010<\/jats:italic><\/jats:sup><jats:italic>Six2<\/jats:italic><jats:sup>\n<jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> double mutant mice showed severe craniofacial defects including midline facial clefting. The complex phenotypes of FND4 patients and of <jats:italic>Six1<\/jats:italic><jats:sup>\n<jats:italic>\u2212\/\u2010<\/jats:italic><\/jats:sup><jats:italic>Six2<\/jats:italic><jats:sup>\n<jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mutant mice indicate that Six2 plays crucial roles in distinct cell types at multiple stages of craniofacial morphogenesis. Here we report generation of mice carrying insertions of a pair of loxP sites flanking exon\u20101 of the <jats:italic>Six2<\/jats:italic> gene (<jats:italic>Six2<\/jats:italic><jats:sup>\n<jats:italic>f<\/jats:italic><\/jats:sup> allele) using CRISPR\/Cas9\u2010mediated genome editing. We show that the <jats:italic>Six2<\/jats:italic><jats:sup>\n<jats:italic>f<\/jats:italic><\/jats:sup> allele functions normally and is effectively inactivated by Cre\u2010mediated recombination in vivo. Furthermore, we show that <jats:italic>Six2<\/jats:italic><jats:sup>\n<jats:italic>f\/f<\/jats:italic><\/jats:sup><jats:italic>;Wnt1\u2010Cre<\/jats:italic> mice recapitulated cranial base defects but not neonatal lethality of <jats:italic>Six2<\/jats:italic><jats:sup>\n<jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. These results indicate that <jats:italic>Six2<\/jats:italic><jats:sup>\n<jats:italic>f\/f<\/jats:italic><\/jats:sup> mice enable systematic investigation of cell type\u2010 and stage\u2010specific Six2 function in development and disease.<\/jats:p>","DOI":"10.1002\/dvg.23365","type":"journal-article","created":{"date-parts":[[2020,4,11]],"date-time":"2020-04-11T06:19:41Z","timestamp":1586585981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Generation and characterization of <i>Six2<\/i> conditional mice"],"prefix":"10.1002","volume":"58","author":[{"given":"Chaochang","family":"Li","sequence":"first","affiliation":[{"name":"Division of Developmental Biology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh\u2010Chiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-3600","authenticated-orcid":false,"given":"Yu","family":"Lan","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Division of Plastic Surgery Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Departments of Pediatrics and Surgery University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Shriners Hospitals for Children  Cincinnati Ohio 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