{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:00:10Z","timestamp":1792479610323,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,3,5]],"date-time":"2004-03-05T00:00:00Z","timestamp":1078444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Treacher Collins syndrome (TCS) is a craniofacial disorder that results from mutations in <jats:italic>TCOF1<\/jats:italic>, which encodes the nucleolar protein Treacle. The severity of the clinical features exhibits wide variation and includes hypoplasia of the mandible and maxilla, abnormalities of the external ears and middle ear ossicles, and cleft palate. To determine the in vivo function of Treacle, we previously generated <jats:italic>Tcof1<\/jats:italic> heterozygous mice on a mixed C57BL\/6 and 129 background. These mice exhibited a lethal phenotype, which included abnormal development of the maxilla, absence of the eyes and nasal passages, and neural tube defects. Here, we show that placing the mutation onto different genetic backgrounds has a major effect on the penetrance and severity of the craniofacial and other defects. The offspring exhibit markedly variable strain\u2010dependent phenotypes that range from extremely severe and lethal in a mixed CBA\/Ca and 129 background, to apparently normal and viable in a mixed BALB\/c and 129 background. In the former case, in addition to a profoundly severe craniofacial phenotype, CBA\u2010derived heterozygous mice also exhibited delayed ossification of the long bones, rib fusions, and digit anomalies. The results of our studies indicate that factors in the different genetic backgrounds contribute extensively to the <jats:italic>Tcof1<\/jats:italic> phenotype. Developmental Dynamics 229:907\u2013914, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.20004","type":"journal-article","created":{"date-parts":[[2004,3,23]],"date-time":"2004-03-23T08:41:11Z","timestamp":1080031271000},"page":"907-914","source":"Crossref","is-referenced-by-count":91,"title":["Genetic background has a major effect on the penetrance and severity of craniofacial defects in mice heterozygous for the gene encoding the nucleolar protein treacle"],"prefix":"10.1002","volume":"229","author":[{"given":"Jill","family":"Dixon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael James","family":"Dixon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,3,5]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"96","article-title":"Treacher Collins syndrome: correlation between clinical and genetic linkage studies","volume":"3","author":"Dixon MJ","year":"1994","journal-title":"Clin Dysmorphol"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.7.3.223"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.10.1473"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.33.7.603"},{"key":"e_1_2_6_6_1","first-page":"515","article-title":"The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature termination codon","volume":"60","author":"Edwards SJ","year":"1997","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.12.7088"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.10.1533"},{"key":"e_1_2_6_9_1","volume-title":"Syndromes of the head and neck","author":"Gorlin RJ","year":"1990"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304304200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.18.4347"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.9.3061"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420440211"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng985"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511897948"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1995.01890050009002"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.11.1795"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(97)00082-8"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/160.4.1609"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2273.1981.tb01782.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0007-117X(75)90019-0"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-60"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200010)16:4<315::AID-HUMU4>3.0.CO;2-H"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.7.493"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00100-8"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0296-130"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.8.2569"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120.5.1109"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.7.3110"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.12.1947"}],"container-title":["Developmental Dynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdvdy.20004","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvdy.20004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T22:29:29Z","timestamp":1760394569000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/dvdy.20004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3,5]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1002\/dvdy.20004"],"URL":"https:\/\/doi.org\/10.1002\/dvdy.20004","archive":["Portico"],"relation":{},"ISSN":["1058-8388","1097-0177"],"issn-type":[{"value":"1058-8388","type":"print"},{"value":"1097-0177","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,3,5]]}}}