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We generated a novel murine model with\n                    <jats:italic>Prx1<\/jats:italic>\n                    \u2010driven deletion of\n                    <jats:italic>Alpl<\/jats:italic>\n                    (\n                    <jats:italic>\n                      Alpl\n                      <jats:sup>Prx1\/Prx1<\/jats:sup>\n                    <\/jats:italic>\n                    ) on a global\n                    <jats:italic>Phospho1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    background, circumventing the perinatal lethality associated with dual global deletion and premature death of\n                    <jats:italic>Alpl<\/jats:italic>\n                    global knockouts. Multi\u2010modal spatial phenotyping of the limbs revealed that mice lacking both TNAP and PHOSPHO1 exhibit distinct mineralization defects and altered anatomical structures at postnatal day 1 (PN1) and 3\u2010weeks of age. Although viable, these mice did not thrive due to reduced size; thus further investigations were conducted on mice with heterozygous deletion of TNAP (\n                    <jats:italic>\n                      Alpl\n                      <jats:sup>wt\/Prx1<\/jats:sup>\n                      ;Phospho1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ). Although smaller than wild\u2010types at PN1 and 3 weeks old, these mice preserved gross limb structure and the single, functioning\n                    <jats:italic>Alpl<\/jats:italic>\n                    allele rescued biomineralization loss following dual phosphatase deletion. In 6\u2010week animals, compromised epiphyses and metaphyses were only observed in\n                    <jats:italic>\n                      Alpl\n                      <jats:sup>Prx1\/Prx1<\/jats:sup>\n                    <\/jats:italic>\n                    animals. Conversely, diaphyseal geometry and porosity were altered by\n                    <jats:italic>Phospho1<\/jats:italic>\n                    deletion, compounded in\n                    <jats:italic>\n                      Alpl\n                      <jats:sup>wt\/Prx1<\/jats:sup>\n                      ;Phospho1\n                      <jats:sup>\u2212\/\u2012<\/jats:sup>\n                    <\/jats:italic>\n                    mice, and linked to alterations in collagen configuration, matrix mineralization, and growth plate deformities. Together, our findings support a mechanistic framework for TNAP and PHOSPHO1 in permissive biomineralization, providing critical insights into this fundamental process.\n                  <\/jats:p>","DOI":"10.1002\/advs.77671","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:37:36Z","timestamp":1789018656000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TNAP and PHOSPHO1 Function Synergistically to Afford Critical Control Over the Mineralization of the Postnatal Murine Skeleton"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3352-4946","authenticated-orcid":false,"given":"Lucie E.","family":"Bourne","sequence":"first","affiliation":[{"name":"Centre For Lifelong Health School of Applied Sciences University of Brighton  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5449-358X","authenticated-orcid":false,"given":"Aikta","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5609-8009","authenticated-orcid":false,"given":"Scott","family":"Dillon","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Keen","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5263-8557","authenticated-orcid":false,"given":"Soher N.","family":"Jayash","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh  Midlothian UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Crump","sequence":"additional","affiliation":[{"name":"Centre For Lifelong Health School of Applied Sciences University of Brighton  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3411-1684","authenticated-orcid":false,"given":"Lucinda A.E.","family":"Evans","sequence":"additional","affiliation":[{"name":"Centre For Lifelong Health School of Applied Sciences University of Brighton  Brighton UK"},{"name":"Faculty of Life Sciences &amp; Medicine Kings College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4025-3160","authenticated-orcid":false,"given":"Maya","family":"Karmali","sequence":"additional","affiliation":[{"name":"Centre For Lifelong Health School of Applied Sciences University of Brighton  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8268-1229","authenticated-orcid":false,"given":"Worachet","family":"Promruk","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh  Midlothian UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6859-5897","authenticated-orcid":false,"given":"Claire E.","family":"Clarkin","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-6380","authenticated-orcid":false,"given":"Sonoko","family":"Narisawa","sequence":"additional","affiliation":[{"name":"Human Genetics Program Sanford Burnham Prebys Medical Discovery Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6795-0383","authenticated-orcid":false,"given":"Louise","family":"Stephen","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh  Midlothian UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3444-0576","authenticated-orcid":false,"given":"Brian L.","family":"Foster","sequence":"additional","affiliation":[{"name":"Division of Biosciences College of Dentistry The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-2671","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Mill\u00e1n","sequence":"additional","affiliation":[{"name":"Human Genetics Program Sanford Burnham Prebys Medical Discovery Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4970-4039","authenticated-orcid":false,"given":"Colin","family":"Farquharson","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh  Midlothian UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8492-9778","authenticated-orcid":false,"given":"Katherine A.","family":"Staines","sequence":"additional","affiliation":[{"name":"Centre For Lifelong Health School of Applied Sciences University of Brighton  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a031229","article-title":"Mechanism of Bone Mineralization","volume":"8","author":"Murshed M.","year":"2018","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.04.003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","DOI":"10.1002\/jbm4.10202","article-title":"How To Build a Bone: PHOSPHO1, Biomineralization, and Beyond","volume":"3","author":"Dillon S.","year":"2019","journal-title":"JBMR Plus"},{"key":"e_1_2_11_5_1","first-page":"489","article-title":"Stereospecific Inhibition of Alkaline Phosphatase by L\u2010tetramisole Prevents in Vitro Cartilage Calcification","volume":"43","author":"Fallon M. 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