{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:46:59Z","timestamp":1793065619233,"version":"4.5.0"},"reference-count":76,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,22]]},"abstract":"<jats:p>\n                    Hypochondroplasia (HCH) is a mild dwarfism caused by missense mutations in fibroblast growth factor receptor 3 (FGFR3), with the majority of cases resulting from a heterozygous p.Asn540Lys gain-of-function mutation. Here, we report the generation and characterization of the first mouse model (\n                    <jats:italic>\n                      Fgfr3\n                      <jats:sup>Asn534Lys\/+<\/jats:sup>\n                    <\/jats:italic>\n                    ) of HCH to our knowledge.\n                    <jats:italic>\n                      Fgfr3\n                      <jats:sup>Asn534Lys\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibited progressive dwarfism and impairment of the synchondroses of the cranial base, resulting in defective formation of the foramen magnum. The appendicular and axial skeletons were both severely affected and we demonstrated an important role of FGFR3 in regulation of cortical and trabecular bone structure. Trabecular bone mineral density (BMD) of long bones and vertebral bodies was decreased, but cortical BMD increased with age in both tibiae and femurs. These results demonstrate that bones in\n                    <jats:italic>\n                      Fgfr3\n                      <jats:sup>Asn534Lys\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice, due to FGFR3 activation, exhibit some characteristics of osteoporosis. The present findings emphasize the detrimental effect of gain-of-function mutations in the\n                    <jats:italic>Fgfr3<\/jats:italic>\n                    gene on long bone modeling during both developmental and aging processes, with potential implications for the management of elderly patients with hypochondroplasia and osteoporosis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.168796","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T14:05:15Z","timestamp":1687356315000},"source":"Crossref","is-referenced-by-count":11,"title":["Hypochondroplasia gain-of-function mutation in FGFR3 causes defective bone mineralization in mice"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1988-9458","authenticated-orcid":true,"given":"L\u00e9a","family":"Loisay","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8381-5381","authenticated-orcid":true,"given":"Davide","family":"Komla-Ebri","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory, Department of Metabolism Digestion and Reproduction, Imperial College London, London, United Kingdom."},{"name":"UCB Pharma, Slough, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Morice","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-9613","authenticated-orcid":true,"given":"Yann","family":"Heuz\u00e9","sequence":"additional","affiliation":[{"name":"UMR5199 PACEA, CNRS, MC, Universit\u00e9 de Bordeaux, Pessac, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6415-4856","authenticated-orcid":true,"given":"Camille","family":"Viaut","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"de La Seigli\u00e8re","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-6815","authenticated-orcid":true,"given":"Nabil","family":"Kaci","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7108-9581","authenticated-orcid":true,"given":"Audrey","family":"Lamouroux","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, CHU Arnaud De Villeneuve, Montpellier, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Baujat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR1163, Paris, France."},{"name":"Department of Medical Genetics, French Reference Center for Skeletal Dysplasia, AP-HP, Necker Enfants Malades Hospital, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.H. 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