{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:26:36Z","timestamp":1791206796989,"version":"4.1.0"},"reference-count":47,"publisher":"The Company of Biologists","issue":"5-6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,4,30]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Wolf-Hirschhorn syndrome (WHS) is caused by deletions in the short arm of chromosome 4 (4p) and occurs in about one per 20,000 births. Patients with WHS display a set of highly variable characteristics including craniofacial dysgenesis, mental retardation, speech problems, congenital heart defects, short stature and a variety of skeletal anomalies. Analysis of patients with 4p deletions has identified two WHS critical regions (WHSCRs); however, deletions targeting mouse WHSCRs do not recapitulate the classical WHS defects, and the genes contributing to WHS have not been conclusively established. Recently, the human FGFRL1 gene, encoding a putative fibroblast growth factor (FGF) decoy receptor, has been implicated in the craniofacial phenotype of a WHS patient. Here, we report that targeted deletion of the mouse Fgfrl1 gene recapitulates a broad array of WHS phenotypes, including abnormal craniofacial development, axial and appendicular skeletal anomalies, and congenital heart defects. Fgfrl1 null mutants also display a transient foetal anaemia and a fully penetrant diaphragm defect, causing prenatal and perinatal lethality. Together, these data support a wider role for Fgfrl1 in development, implicate FGFRL1 insufficiency in WHS, and provide a novel animal model to dissect the complex aetiology of this human disease.<\/jats:p>","DOI":"10.1242\/dmm.002287","type":"journal-article","created":{"date-parts":[[2009,4,22]],"date-time":"2009-04-22T03:13:48Z","timestamp":1240370028000},"page":"283-294","source":"Crossref","is-referenced-by-count":76,"title":["Multiple congenital malformations of Wolf-Hirschhorn syndrome are recapitulated in<i>Fgfrl1<\/i>null mice"],"prefix":"10.1242","volume":"2","author":[{"given":"Catarina","family":"Catela","sequence":"first","affiliation":[{"name":"European Molecular Biology Laboratory, Mouse Biology Unit, 00015 Monterotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bilbao-Cortes","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, Mouse Biology Unit, 00015 Monterotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esfir","family":"Slonimsky","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, Mouse Biology Unit, 00015 Monterotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paschalis","family":"Kratsios","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, Mouse Biology Unit, 00015 Monterotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, Mouse Biology Unit, 00015 Monterotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"te Welscher","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, Mouse Biology Unit, 00015 Monterotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042500051207500_b1-0020283","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1093\/nar\/27.17.e16","article-title":"Simplified generation of targeting constructs using ET recombination","volume":"27","author":"Angrand","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"2021042500051207500_b2-0020283","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.1111\/j.1742-4658.2007.06143.x","article-title":"Mice with a targeted disruption of the Fgfrl1 gene die at birth due to alterations in the diaphragm","volume":"274","author":"Baertschi","year":"2007","journal-title":"FEBS J"},{"key":"2021042500051207500_b3-0020283","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0065-3101(23)00074-9","article-title":"Wolf-Hirschhorn (4p-) syndrome","volume":"48","author":"Battaglia","year":"2001","journal-title":"Adv. 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