{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:41:33Z","timestamp":1789123293376,"version":"build-2803163510"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T00:00:00Z","timestamp":1692057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["AR056645"],"award-info":[{"award-number":["AR056645"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["AR066261"],"award-info":[{"award-number":["AR066261"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["AR070542"],"award-info":[{"award-number":["AR070542"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK11794"],"award-info":[{"award-number":["DK11794"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK113039"],"award-info":[{"award-number":["DK113039"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Activating parathyroid hormone (PTH)\/PTH\u2010related Peptide (PTHrP) receptor (PTH1R) mutations causes Jansen's metaphyseal chondrodysplasia (JMC), a rare disease characterized by growth plate abnormalities, short stature, and PTH\u2010independent hypercalcemia. Previously generated transgenic JMC mouse models, in which the human\n                    <jats:italic>PTH1R<\/jats:italic>\n                    allele with the H223R mutation (\n                    <jats:italic>H223R\u2010PTH1R<\/jats:italic>\n                    ) is expressed in osteoblasts via type Ia1 collagen or DMP1 promoters cause excess bone mass, while expression of the mutant allele via the type IIa1 collagen promoter results in only minor growth plate changes. Thus, neither transgenic JMC model adequately recapitulates the human disease. We therefore generated \u201chumanized\u201d JMC mice in which the\n                    <jats:italic>H223R\u2010PTH1R<\/jats:italic>\n                    allele was expressed via the endogenous mouse\n                    <jats:italic>Pth1r<\/jats:italic>\n                    promoter and, thus, in all relevant target tissues. Founders with the H223R allele typically died within 2\u2009months without reproducing; several mosaic male founders, however, lived longer and produced F1\n                    <jats:italic>H223R\u2010PTH1R<\/jats:italic>\n                    offspring, which were small and exhibited marked growth plate abnormalities. Serum calcium and phosphate levels of the mutant mice were not different from wild\u2010type littermates, but serum PTH and P1NP were reduced significantly, while CTX\u20101 and CTX\u20102 were slightly increased. Histological and RNAscope analyses of the mutant tibial growth plates revealed markedly expanded zones of type II collagen\u2010positive, proliferating\/prehypertrophic chondrocytes, abundant apoptotic cells in the growth plate center and a progressive reduction of type X collagen\u2010positive hypertrophic chondrocytes and primary spongiosa. The \u201chumanized\u201d\n                    <jats:italic>H223R\u2010PTH1R<\/jats:italic>\n                    mice are likely to provide a more suitable model for defining the JMC phenotype and for assessing potential treatment options for this debilitating disease of skeletal development and mineral ion homeostasis. \u00a9 2023 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10802","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T04:35:33Z","timestamp":1692074133000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Substantially Delayed Maturation of Growth Plate Chondrocytes in \u201cHumanized\u201d\n                    <scp>\n                      <i>PTH1R<\/i>\n                    <\/scp>\n                    Mice with the\n                    <scp>H223R<\/scp>\n                    Mutation of Jansen's Disease"],"prefix":"10.1093","volume":"7","author":[{"given":"Monica","family":"Reyes","sequence":"first","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damla","family":"Firat","sequence":"additional","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hanna","sequence":"additional","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery University of Pennsylvania, Perelman Medical School  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bruce","sequence":"additional","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Shvedova","sequence":"additional","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernestina","family":"Schipani","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery University of Pennsylvania, Perelman Medical School  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2163-5772","authenticated-orcid":false,"given":"Thomas J.","family":"Gardella","sequence":"additional","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7491-0515","authenticated-orcid":false,"given":"Harald","family":"J\u00fcppner","sequence":"additional","affiliation":[{"name":"Endocrine Unit Massachusetts General Hospital and Harvard Medical School  Boston MA USA"},{"name":"Pediatric Nephrology Unit Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,15]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"253","article-title":"\u00dcber atypische Chondrodystrophie (Achondroplasie) und \u00fcber eine noch nicht beschriebene angeborene Wachstumsst\u00f6rung des Knochensystems: Metaphys\u00e4re Dysostosis","volume":"61","author":"Jansen M","year":"1934","journal-title":"Zeitschr Orthop Chir"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7701349"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199609053351004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-397166-1.00040-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00332"},{"key":"e_1_2_9_7_1","first-page":"851","article-title":"Constitutive activation of the cAMP signaling pathway by parathyroid hormone (PTH)\/PTH\u2010related peptide (PTHrP) receptors mutated at the two loci for Jansen's metaphyseal chondrodysplasia","volume":"11","author":"Schipani E","year":"1997","journal-title":"Mol Endocrinol"},{"key":"e_1_2_9_8_1","first-page":"269","volume-title":"Pediatric Diseases Related to Calcium","author":"Frame B","year":"1980"},{"key":"e_1_2_9_9_1","first-page":"1173","volume-title":"Vitamin D, Basic Research and its Clinical Application","author":"Rao DS","year":"1979"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.385"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-013-1014-3"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.136.2.7835276"},{"key":"e_1_2_9_13_1","first-page":"1038","volume-title":"Endocrinology","author":"Maes C","year":"2016"},{"key":"e_1_2_9_14_1","first-page":"969","volume-title":"Endocrinology","author":"Gardella TJ","year":"2016"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1012717"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.81.10.3584"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01957529"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3082"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2054"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0036"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.9.8756569"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.4.8103"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2014-1129"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3913"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11296"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002942"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.13689"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqac054"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1400-x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30137-x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0353-2"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2014.06.013"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1119-7_6"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.02.008"},{"issue":"1","key":"e_1_2_9_35_1","first-page":"F042","article-title":"A mouse model of Jansen metaphyseal chondrodysplasia (JMC): introduction of the H223R mutation into the murine PTH\/PTHrP receptor gene results in delayed endochondral bone formation","volume":"19","author":"Fr\u00f6hlich L","year":"2004","journal-title":"J Bone Mineral Research"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat9356"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.934301"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200419383"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.3.277"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.663"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130126"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T09:58:21Z","timestamp":1710410301000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/7\/10\/n\/a\/7612306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,15]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/jbm4.10802"],"URL":"https:\/\/doi.org\/10.1002\/jbm4.10802","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JBM4.10802\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10802\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10802\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10802\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10802\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10802\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JBM4.10802\/v3\/decision1","asserted-by":"object"}]},"ISSN":["2473-4039","2473-4039"],"issn-type":[{"value":"2473-4039","type":"print"},{"value":"2473-4039","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,15]]},"assertion":[{"value":"2023-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10802"}}