{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T01:53:21Z","timestamp":1781229201906,"version":"3.54.1"},"reference-count":61,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T00:00:00Z","timestamp":1377820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:p>Mouse models provide valuable opportunities for probing the underlying pathology of human birth defects. By using an <jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea\u2010based screen for recessive mutations affecting craniofacial anatomy, we isolated a mouse strain, <jats:italic>Dogface\u2010like<\/jats:italic> (<jats:italic>DL<\/jats:italic>), with abnormal skull and snout morphology. Examination of the skull indicated that these mice developed craniosynostosis of the lambdoid suture. Further analysis revealed skeletal defects related to the pathology of basal cell nevus syndrome (BCNS) including defects in development of the limbs, scapula, ribcage, secondary palate, cranial base, and cranial vault. In humans, BCNS is often associated with mutations in the Hedgehog receptor <jats:italic>PTCH1<\/jats:italic> and genetic mapping in <jats:italic>DL<\/jats:italic> identified a point mutation at a splice donor site in <jats:italic>Ptch1<\/jats:italic>. By using genetic complementation analysis we determined that <jats:italic>DL<\/jats:italic> is a hypomorphic allele of <jats:italic>Ptch1<\/jats:italic>, leading to increased Hedgehog signaling. Two aberrant transcripts are generated by the mutated <jats:italic>Ptch1<jats:sup>DL<\/jats:sup><\/jats:italic> gene, which would be predicted to reduce significantly the levels of functional Patched1 protein. This new <jats:italic>Ptch1<\/jats:italic> allele broadens the mouse genetic reagents available to study the Hedgehog pathway and provides a valuable means to study the underlying skeletal abnormalities in BCNS. In addition, these results strengthen the connection between elevated Hedgehog signaling and craniosynostosis. genesis 51:677\u2013689. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/dvg.22416","type":"journal-article","created":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T15:10:12Z","timestamp":1375110612000},"page":"677-689","source":"Crossref","is-referenced-by-count":30,"title":["The <i>Ptch1<sup>DL<\/sup><\/i> mouse: A new model to study lambdoid craniosynostosis and basal cell nevus syndrome\u2010associated skeletal defects"],"prefix":"10.1002","volume":"51","author":[{"given":"Weiguo","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Craniofacial Biology and Cell and Developmental Biology University of Colorado Anschutz Medical Campus Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Biology and Cell and Developmental Biology University of Colorado Anschutz Medical Campus Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Clouthier","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Biology and Cell and Developmental Biology University of Colorado Anschutz Medical Campus Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Niswander","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Howard Hughes Medical Institute University of Colorado Anschutz Medical Campus Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Biology and Cell and Developmental Biology University of Colorado Anschutz Medical Campus Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.002709"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2008.01.001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.08.011"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.9.2214"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2003.10.039"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.091785"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.037507"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds409"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20853"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.06.008"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.04.021"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.006262"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.05.030"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10208"},{"key":"e_1_2_6_16_1","volume-title":"GeneReviews\u2122 [Internet]","author":"Evans GD","year":"2010"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(03)00209-4"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5329.1109"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(08)00602-9"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0598-619"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1998.19310081.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-012-1844-3"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.13"},{"key":"e_1_2_6_24_1","first-page":"956","article-title":"Gorlin syndrome: Unusual manifestations in the sella turcica and the sphenoidal sinus","volume":"19","author":"Iwanaga S","year":"1998","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_6_25_1","unstructured":"Jax.2011.Protocol for genotyping. 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