{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:41:51Z","timestamp":1790361711367,"version":"4.1.0"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Caen University Hospital Reference Center for Rare diseases of Calcium and Phosphate Metabolism","award":["none"],"award-info":[{"award-number":["none"]}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["R01 AR080062,R01 AR083245,P30 AR069619"],"award-info":[{"award-number":["R01 AR080062,R01 AR083245,P30 AR069619"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,16]]},"abstract":"<jats:p>\n                    Achondroplasia, the most prevalent short-stature disorder, is caused by missense variants overactivating the fibroblast growth factor receptor 3 (FGFR3). As current surgical and pharmaceutical treatments only partially improve some disease features, we sought to explore a genetic approach. We show that an enhancer located 29 kb upstream of mouse\n                    <jats:italic>Fgfr3<\/jats:italic>\n                    (\n                    <jats:italic>\u201329E<\/jats:italic>\n                    ) is sufficient to confer a transgenic mouse reporter with a domain of expression in cartilage matching that of\n                    <jats:italic>Fgfr3<\/jats:italic>\n                    . Its CRISPR\/Cas9-mediated deletion in otherwise WT mice reduced\n                    <jats:italic>Fgfr3<\/jats:italic>\n                    expression in this domain by half without causing adverse phenotypes. Importantly, its deletion in mice harboring the ortholog of the most common human achondroplasia variant largely normalized long bone and vertebral body growth, markedly reduced spinal canal and foramen magnum stenosis, and improved craniofacial defects. Consequently, mouse achondroplasia is no longer lethal, and adults are overall healthy. These findings, together with high conservation of\n                    <jats:italic>\u201329E<\/jats:italic>\n                    in humans, open a path to develop genetic therapies for people with achondroplasia.\n                  <\/jats:p>","DOI":"10.1172\/jci184929","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T14:00:44Z","timestamp":1736949644000},"source":"Crossref","is-referenced-by-count":5,"title":["Fgfr3 enhancer deletion markedly improves all skeletal features in a mouse model of achondroplasia"],"prefix":"10.1172","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4085-7661","authenticated-orcid":true,"given":"Marco","family":"Angelozzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Molin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-9860","authenticated-orcid":true,"given":"Anirudha","family":"Karvande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"Fern\u00e1ndez-Iglesias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Whipple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Bloh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Lefebvre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24479"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1086\/508433"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22597"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2244114.057"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61787"},{"issue":"2","key":"B6","first-page":"368","article-title":"Achondroplasia is defined by recurrent G380R mutations of FGFR3","volume":"56","author":"Bellus","year":"1995","journal-title":"Am J Hum Genet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/ng0496-390"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0972-6"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-7020-4086-3.00036-9"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13542"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.115872"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1914"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-012-2126-x"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2023.05.008"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115579"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115573"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31541-5"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102258"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-023-02705-9"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(23)00265-1"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10258"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0479-7"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nature11243"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24345-9"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.056"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111315"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.06.013"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv688"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2019152118"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba7612"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.46.27711"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1242\/dev.105.4.707"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.15.1908"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.8.4455"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14602"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36456-3"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.02.005"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.176"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.3.1113"},{"key":"B40","unstructured":"Unger S, et al. 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