{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:19:15Z","timestamp":1787768355220,"version":"build-2784847793"},"reference-count":54,"publisher":"The Company of Biologists","issue":"8","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Facial paralysis, hearing loss and potentially lethal raised intracranial pressure are primary symptoms of sclerosteosis, an ultra-rare, autosomal recessive high bone mass (HBM) condition that predominantly manifests in skull pathologies. Non-invasive treatment remains an unmet clinical need. Recently, PORCN inhibition has been shown to reduce bone mass in young Sost-deficient (Sost\u2212\/\u2212) mice. In this paper, we characterised sclerosteosis skull pathologies at later adult stages using a Sost\u2212\/\u2212 mouse model, with a view to drug efficacy evaluation. This revealed that male and female 9-month-old Sost\u2212\/\u2212 mice recapitulate the skull overgrowth and neural impingement of human sclerosteosis. We observed that the foramen magnum was narrowed in Sost\u2212\/\u2212 mice, and that parietal bone mass and thickness were significantly elevated. Otosclerosis was apparent, and animals exhibited significant hearing loss at age 8-9 months. Further, prominent mandibles highlighted hyperostosis in the jaw. Sexual dimorphism was also evident in the Sost\u2212\/\u2212 mice, underscoring the importance of including both sexes in HBM studies. This study provides new insight into Sost\u2212\/\u2212-skull-related pathology and further validates Sost\u2212\/\u2212 mice as a valuable model for investigating potential treatments for sclerosteosis and other HBM related conditions.<\/jats:p>","DOI":"10.1242\/dmm.052839","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:32:43Z","timestamp":1787765563000},"source":"Crossref","is-referenced-by-count":0,"title":["Characterising skull pathologies in the\n                    <i>Sost<\/i>\n                    -deficient mouse for preclinical evaluation of sclerosteosis treatments"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7460-7292","authenticated-orcid":false,"given":"Timothy J.","family":"Dreyer","sequence":"first","affiliation":[{"name":"The Royal Veterinary College 1 Skeletal Biology Group, Department of Comparative Biomedical Sciences , , London NW1 0TU,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Gouldie","sequence":"additional","affiliation":[{"name":"The Royal Veterinary College 1 Skeletal Biology Group, Department of Comparative Biomedical Sciences , , London NW1 0TU,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3679-2008","authenticated-orcid":false,"given":"Jacob A. C.","family":"Keen","sequence":"additional","affiliation":[{"name":"The Royal Veterinary College 1 Skeletal Biology Group, Department of Comparative Biomedical Sciences , , London NW1 0TU,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Salmon","sequence":"additional","affiliation":[{"name":"Bruker 2 , 2550 Kontich ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9979-8694","authenticated-orcid":false,"given":"Gill","family":"Holdsworth","sequence":"additional","affiliation":[{"name":"UCB Pharma 3 , Slough SL1 3WE ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3861-998X","authenticated-orcid":false,"given":"Andrew A.","family":"Pitsillides","sequence":"additional","affiliation":[{"name":"The Royal Veterinary College 1 Skeletal Biology Group, Department of Comparative Biomedical Sciences , , London NW1 0TU,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3974-8895","authenticated-orcid":false,"given":"Scott J.","family":"Roberts","sequence":"additional","affiliation":[{"name":"The Royal Veterinary College 1 Skeletal Biology Group, Department of Comparative Biomedical Sciences , , London NW1 0TU,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"2026082613323386400_DMM052839C1","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00223-019-00648-4","article-title":"Effects of long-term sclerostin deficiency on trabecular bone mass and adaption to limb loading differ in male and female mice","volume":"106","author":"Albiol","year":"2020","journal-title":"Calcif. 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