{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T03:43:06Z","timestamp":1771904586895,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,20]]},"group-title":"Developmental Biology","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>TBCK syndrome is a severe degenerative leukoencephalopathy with multisystem involvement. Neurodevelopmental, craniofacial, and pulmonary challenges are among the topmost effects on these children. TBCK has been implicated in endo-lysosomal regulation, RNA transport, and mTOR-associated pathways, all of which are critical for the development of mineralized tissue. Although craniofacial abnormalities can be clinically apparent, conventional imaging approaches may overlook subtle defects in mineral quality.<\/jats:p>\n                <jats:p>\n                  Here, we apply our multimodal framework to investigate the mineralization of enamel, dentin, and alveolar bone in a\n                  <jats:italic>Tbck<\/jats:italic>\n                  knockout mouse model. This is the first time our multimodal framework will be applied to a genetic condition. Using micro-computed tomography (microCT), histology, nanoindentation, energy-dispersive spectroscopy, and Raman spectroscopy, we identify tissue- and stage-dependent mineral effects undetected by microCT alone.\n                  <jats:italic>Tbck<\/jats:italic>\n                  loss resulted in differences in enamel and dentin element compositions as early as secretory and transition stages, while mechanical properties remained undetected until maturation stage.\n                <\/jats:p>\n                <jats:p>\n                  Notably,\n                  <jats:italic>Tbck<\/jats:italic>\n                  knockout enamel exhibited reduced calcium and phosphorus content, along with increased carbon content during early mineralization, consistent with the retained organic matrix. Additionally, marked and opposing alterations in magnesium and iron levels began at the secretory stage. Together, these findings define a previously unrecognized mineralization signature associated with TBCK deficiency and establish multimodal hard-tissue analysis as a sensitive approach for detecting early craniofacial phenotypes in rare genetic disorders.\n                <\/jats:p>","DOI":"10.64898\/2026.02.18.706703","type":"posted-content","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T16:55:18Z","timestamp":1771606518000},"source":"Crossref","is-referenced-by-count":0,"title":["Unique mineralization pattern revealed in TBCK syndrome mouse model"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-185X","authenticated-orcid":false,"given":"Kaitlin A.","family":"Katsura","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, 19104, USA"},{"name":"Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA"},{"name":"Department of Orofacial Sciences, University of California, San Francisco, CA, 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5981-7430","authenticated-orcid":false,"given":"Yuchen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Materials Science and Engineering, School of Engineering and Applied Science, University of Pennsylvania, PA, 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5382-2493","authenticated-orcid":false,"given":"Marius","family":"Didziokas","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, University College London, London, WC1E 6BT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0882-4584","authenticated-orcid":false,"given":"Nir Z.","family":"Badt","sequence":"additional","affiliation":[{"name":"Department of Earth and Environmental Sciences, University of Pennsylvania, PA, 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Dougherty","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-879X","authenticated-orcid":false,"given":"Kyle H.","family":"Vining","sequence":"additional","affiliation":[{"name":"Materials Science and Engineering, School of Engineering and Applied Science, University of Pennsylvania, PA, 19104, USA"},{"name":"Preventive and Restorative Dentistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA"},{"name":"Center for Innovation and Precision Dentistry, University of Pennsylvania, Philadelphia, PA, 19104, 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