{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T02:53:28Z","timestamp":1773975208003,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T00:00:00Z","timestamp":1456272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"American Heart","award":["0950041G"],"award-info":[{"award-number":["0950041G"]}]},{"DOI":"10.13039\/100000912","name":"March of Dimes","doi-asserted-by":"crossref","award":["6-FY10-339"],"award-info":[{"award-number":["6-FY10-339"]}],"id":[{"id":"10.13039\/100000912","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["RO1 HL119946"],"award-info":[{"award-number":["RO1 HL119946"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:bold><jats:styled-content>Background:<\/jats:styled-content><\/jats:bold> <jats:italic>Fras1<\/jats:italic> encodes an extracellular matrix protein that is critical for the establishment of the epidermal basement membrane during gestation. In humans, mutations in <jats:italic>FRAS1<\/jats:italic> cause Fraser Syndrome (FS), a pleiotropic condition with many clinical presentations such as limb, eye, kidney, and craniofacial deformations. Many of these defects are mimicked by loss of <jats:italic>Fras1<\/jats:italic> in mice, and are preceded by the formation of epidermal blisters <jats:italic>in utero<\/jats:italic>. <jats:bold><jats:styled-content>Results:<\/jats:styled-content><\/jats:bold> In this study, we identified a novel ENU\u2010derived <jats:italic>rounded foot<\/jats:italic> (<jats:italic>rdf<\/jats:italic>) mouse mutant with highly penetrant hindlimb soft\u2010tissue syndactyly, among other structural defects. Mapping and sequencing revealed that <jats:italic>rdf<\/jats:italic> is a novel loss\u2010of\u2010function nonsense allele of <jats:italic>Fras1<\/jats:italic> (<jats:italic>Fras1<\/jats:italic><jats:sup><jats:italic>rdf<\/jats:italic><\/jats:sup>). Focusing on the limb, we found that the <jats:italic>Fras1<\/jats:italic><jats:sup><jats:italic>rdf<\/jats:italic><\/jats:sup> syndactyly phenotype originates from loss of interdigital cell death (ICD). Despite normal expression of bone morphogenetic protein (BMP) ligands and their receptors, the BMP downstream target gene <jats:italic>Msx2<\/jats:italic>, which is also necessary and sufficient to promote ICD, was down\u2010regulated in the interdigital regions of <jats:italic>Fras1<\/jats:italic><jats:sup><jats:italic>rdf<\/jats:italic><\/jats:sup> hindlimb buds. <jats:bold><jats:styled-content>Conclusions:<\/jats:styled-content><\/jats:bold> The close correlation between limb bud epidermal blistering, decreased <jats:italic>Msx2<\/jats:italic> expression, and reduced ICD in the <jats:italic>Fras1<\/jats:italic><jats:sup><jats:italic>rdf<\/jats:italic><\/jats:sup> hindlimb buds suggests that epithelium detachment from the mesenchyme may create a physical gap that interrupts the transmission of BMP, among other signals, resulting in soft tissue syndactyly. <jats:italic>Developmental Dynamics 245:497\u2013507, 2016<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.24389","type":"journal-article","created":{"date-parts":[[2016,1,27]],"date-time":"2016-01-27T03:50:40Z","timestamp":1453866640000},"page":"497-507","source":"Crossref","is-referenced-by-count":13,"title":["Syndactyly in a novel <i>Fras1<\/i><sup><i>rdf<\/i><\/sup> mutant results from interruption of signals for interdigital apoptosis"],"prefix":"10.1002","volume":"245","author":[{"given":"Elizabeth A.","family":"Hines","sequence":"first","affiliation":[{"name":"Laboratory of Genetics University of Wisconsin Madison  WI 53706"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie M.","family":"Verheyden","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics University of Wisconsin Madison  WI 53706"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber J.","family":"Lashua","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics University of Wisconsin Madison  WI 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