{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:55:14Z","timestamp":1790434514794,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P01 HD078233"],"award-info":[{"award-number":["P01 HD078233"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01 DE022988"],"award-info":[{"award-number":["R01 DE022988"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["T32 DC000018"],"award-info":[{"award-number":["T32 DC000018"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2021,4]]},"abstract":"Objectives<\/jats:title>To characterize tracheal cartilage morphology in mouse models of fibroblast growth factor receptor (Fgfr2<\/jats:italic>)\u2010related craniosynostosis syndromes. To establish relationships between specific Fgfr2<\/jats:italic> mutations and tracheal cartilaginous sleeve (TCS) phenotypes in these mouse models.<\/jats:p><\/jats:sec>Methods<\/jats:title>Postnatal day 0 knock\u2010in mouse lines with disease\u2010specific genetic variations in the Fgfr2<\/jats:italic> gene (Fgfr2<\/jats:italic>C342Y\/C342Y<\/jats:sup>, Fgfr2<\/jats:italic>C342Y\/+<\/jats:sup>, Fgfr2<\/jats:italic>+\/Y394C<\/jats:sup>, Fgfr2<\/jats:italic>+\/S252W<\/jats:sup>, and Fgfr2<\/jats:italic>+\/P253R<\/jats:sup>) as well as line\u2010specific controls were utilized. Tracheal cartilage morphology as measured by gross analyses, microcomputed tomography (\u03bcCT), and histopathology were compared using Chi\u2010squared and single\u2010factor analysis of variance statistical tests.<\/jats:p><\/jats:sec>Results<\/jats:title>A greater proportion of rings per trachea were abnormal in Fgfr2<\/jats:italic>C342Y\/+<\/jats:sup> tracheas (63%) than Fgfr2<\/jats:italic>+\/S252W<\/jats:sup> (17%), Fgfr2<\/jats:italic>+\/P253R<\/jats:sup> (17%), Fgfr2<\/jats:italic>+\/Y394C<\/jats:sup> (12%), and controls (10%) (P<\/jats:italic>\u2009<\u2009.001 for each vs. Fgfr2<\/jats:italic>C342Y\/+<\/jats:sup>). TCS segments were found only in Fgfr2<\/jats:italic>C342Y\/C342Y<\/jats:sup> (100%) and Fgfr2<\/jats:italic>C342Y\/+<\/jats:sup> (72%) tracheas. Cricoid and first\u2010tracheal ring fusion was noted in all Fgfr2<\/jats:italic>C342Y\/C342Y<\/jats:sup> and 94% of Fgfr2<\/jats:italic>C342Y\/+<\/jats:sup> samples. The Fgfr2<\/jats:italic>C342Y\/C342Y<\/jats:sup> and Fgfr2<\/jats:italic>C342Y\/+<\/jats:sup> groups were found to have greater areas and volumes of cartilage than other lines on gross analysis and \u03bcCT. Histologic analyses confirmed TCS among the Fgfr2<\/jats:italic>C342Y\/C342Y<\/jats:sup> and Fgfr2<\/jats:italic>C342Y\/+<\/jats:sup> groups, without appreciable differences in cartilage morphology, cell size, or density; no histologic differences were observed among other Fgfr2<\/jats:italic> lines compared to controls.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>This study found TCS phenotypes only in the Fgfr2<\/jats:italic>C342Y<\/jats:sup> mouse lines. These lines also had increased tracheal cartilage compared to other mutant lines and controls. These data support further study of the Fgfr2<\/jats:italic> mouse lines and the investigation of other Fgfr2<\/jats:italic> variants to better understand their role in tracheal development and TCS formation.<\/jats:p><\/jats:sec>Level of Evidence<\/jats:title>NA Laryngoscope<\/jats:italic>, 131:E1349\u2013E1356, 2021<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.29060","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T17:13:40Z","timestamp":1599239620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genotype\u2013Phenotype Correlation of Tracheal Cartilaginous Sleeves and Fgfr2<\/i> Mutations in Mice"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2297-6376","authenticated-orcid":false,"given":"Austin S.","family":"Lam","sequence":"first","affiliation":[{"name":"Department of Otolaryngology \u2013 Head & Neck Surgery University of Washington School of Medicine Seattle Washington U.S.A."},{"name":"Division of Pediatric Otolaryngology \u2013 Head & Neck Surgery Seattle Children's Hospital Seattle Washington U.S.A."},{"name":"Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine Seattle Washington U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9262-2792","authenticated-orcid":false,"given":"Carrie C.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2013 Head & Neck Surgery University of Washington School of Medicine Seattle Washington U.S.A."},{"name":"Division of Pediatric Otolaryngology \u2013 Head & Neck Surgery Seattle Children's Hospital Seattle Washington U.S.A."},{"name":"Current address: Divisions of Otolaryngology \u2013 Head and Neck Surgery, and Pediatric Surgery, Department of Surgery University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail H.","family":"Deutsch","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington School of Medicine Seattle Washington U.S.A."},{"name":"Department of Pathology Seattle Children's Hospital Seattle Washington U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York City New York U.S.A."},{"name":"Current address: Center for Personalized Cancer Therapy University of Massachusetts Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-3997","authenticated-orcid":false,"given":"Jonathan A.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2013 Head & Neck Surgery University of Washington School of Medicine Seattle Washington U.S.A."},{"name":"Division of Pediatric Otolaryngology \u2013 Head & Neck Surgery Seattle Children's Hospital Seattle Washington U.S.A."},{"name":"Craniofacial Center Seattle Children's Hospital Seattle Washington U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York City New York U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethylin W.","family":"Jabs","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York City New York U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute, Center for Developmental Biology and 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