{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:12:24Z","timestamp":1790475144050,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Familial tumoral calcinosis is characterized by ectopic calcifications due to persistent hyperphosphatemia. The most common genetic cause of the disease is mutations in GALNT3, encoding a glycosyltransferase involved in a posttranslational modification of fibroblast growth factor 23 (FGF23). The Galnt3 knockout mouse we developed was hyperphosphatemic due to low intact Fgf23 levels, but did not develop any apparent calcifications on a standard rodent diet. We therefore tested the hypothesis that a further challenge with a high phosphate diet could induce ectopic calcifications in Galnt3 knockout mice. Mice were fed either normal (0.6%) or high (1.65%) phosphate diet for 20 weeks beginning from weaning at 3 weeks. The high phosphate diet did not affect serum phosphorus concentration. However, regardless of the dietary phosphate contents, serum phosphorus levels were consistently elevated in Galnt3 knockout mice. The mice on the high phosphate diet had slightly low serum calcium, but significantly high alkaline phosphatase, parathyroid hormone (PTH), and calcium in the kidney. Although none of Galnt3 knockout mice on the normal phosphate diet developed calcifications, calcifications appeared in approximately one-half of the mice on the high phosphate diet by 12 weeks. Calcified masses were most often found around the neck and on the back and as large as 9.9\u2009mm in length. These data indicate that dietary phosphate load has major impact on the development of ectopic calcifications in tumoral calcinosis. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2242","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T12:56:11Z","timestamp":1396356971000},"page":"2017-2023","source":"Crossref","is-referenced-by-count":12,"title":["High Dietary Phosphate Intake Induces Development of Ectopic Calcifications in a Murine Model of Familial Tumoral Calcinosis"],"prefix":"10.1093","volume":"29","author":[{"given":"Shoji","family":"Ichikawa","sequence":"first","affiliation":[{"name":"Department of MedicineIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amie K","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of MedicineIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah R","family":"Padgett","sequence":"additional","affiliation":[{"name":"Department of MedicineIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin M","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of MedicineIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler R","family":"Unsicker","sequence":"additional","affiliation":[{"name":"Department of MedicineIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,4,1]]},"reference":[{"issue":"3","key":"2024020318491971000_jbmr2242-bib-0001","doi-asserted-by":"crossref","first-page":"664","DOI":"10.2106\/JBJS.G.01512","article-title":"Familial tumoral calcinosis: a forty-year follow-up on one family","volume":"91","author":"Carmichael","year":"2009","journal-title":"J Bone Joint Surg Am."},{"issue":"4","key":"2024020318491971000_jbmr2242-bib-0002","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/ajmg.a.33337","article-title":"Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations","volume":"152A","author":"Ichikawa","year":"2010","journal-title":"Am J Med Genet A."},{"key":"2024020318491971000_jbmr2242-bib-0003","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/0002-9343(61)90131-0","article-title":"Heterotopic calcification, hyperphosphatemia and angioid streaks of the retina","volume":"31","author":"McPhaul","year":"1961","journal-title":"Am J Med."},{"issue":"3","key":"2024020318491971000_jbmr2242-bib-0004","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1001\/archopht.1996.01100130337022","article-title":"Ocular tumoral calcinosis. A clinicopathologic study","volume":"114","author":"Ghanchi","year":"1996","journal-title":"Arch Ophthalmol."},{"issue":"6","key":"2024020318491971000_jbmr2242-bib-0005","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1210\/jcem-60-6-1093","article-title":"Genetic transmission of tumoral calcinosis: autosomal dominant with variable clinical expressivity","volume":"60","author":"Lyles","year":"1985","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2024020318491971000_jbmr2242-bib-0006","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/S0022-3476(81)80013-3","article-title":"The syndrome of hyperostosis and hyperphosphatemia","volume":"99","author":"Mikati","year":"1981","journal-title":"J Pediatr."},{"issue":"3","key":"2024020318491971000_jbmr2242-bib-0007","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1148\/radiology.151.3.6718723","article-title":"Tumoral calcinosis, diaphysitis, and hyperphosphatemia","volume":"151","author":"Clarke","year":"1984","journal-title":"Radiology."},{"issue":"3","key":"2024020318491971000_jbmr2242-bib-0008","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1097\/01241398-198805000-00016","article-title":"Hyperostosis with hyperphosphatemia: a case report and review of the literature","volume":"8","author":"Talab","year":"1988","journal-title":"J Pediatr Orthop."},{"issue":"7","key":"2024020318491971000_jbmr2242-bib-0009","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s00198-008-0775-z","article-title":"A case of familial tumoral calcinosis\/hyperostosis-hyperphosphatemia syndrome due to a compound heterozygous mutation in GALNT3 demonstrating new phenotypic features","volume":"20","author":"Dumitrescu","year":"2009","journal-title":"Osteoporos Int."},{"issue":"1","key":"2024020318491971000_jbmr2242-bib-0010","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00256-009-0808-5","article-title":"Familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are different manifestations of the same disease: novel missense mutations in GALNT3","volume":"39","author":"Joseph","year":"2010","journal-title":"Skeletal Radiol."},{"issue":"1","key":"2024020318491971000_jbmr2242-bib-0011","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00109-004-0610-8","article-title":"Identification of a recurrent mutation in GALNT3 demonstrates that hyperostosis-hyperphosphatemia syndrome and familial tumoral calcinosis are allelic disorders","volume":"83","author":"Frishberg","year":"2005","journal-title":"J Mol Med."},{"issue":"10","key":"2024020318491971000_jbmr2242-bib-0012","doi-asserted-by":"crossref","first-page":"5523","DOI":"10.1210\/jc.2005-0301","article-title":"A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis","volume":"90","author":"Araya","year":"2005","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2024020318491971000_jbmr2242-bib-0013","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1093\/hmg\/ddi034","article-title":"An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia","volume":"14","author":"Benet-Pag\u00e8s","year":"2005","journal-title":"Hum Mol Genet."},{"issue":"2","key":"2024020318491971000_jbmr2242-bib-0014","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00439-005-0026-8","article-title":"A novel homozygous missense mutation in FGF23 causes Familial Tumoral Calcinosis associated with disseminated visceral calcification","volume":"118","author":"Chefetz","year":"2005","journal-title":"Hum Genet."},{"issue":"4","key":"2024020318491971000_jbmr2242-bib-0015","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1210\/jc.2004-2238","article-title":"A novel recessive mutation in fibroblast growth factor-23 causes familial tumoral calcinosis","volume":"90","author":"Larsson","year":"2005","journal-title":"J Clin Endocrinol Metab."},{"issue":"11","key":"2024020318491971000_jbmr2242-bib-0016","doi-asserted-by":"crossref","first-page":"6500","DOI":"10.1073\/pnas.101545198","article-title":"Cloning, characterization of FGF23 as a causative factor of tumor-induced osteomalacia","volume":"98","author":"Shimada","year":"2001","journal-title":"Proc Natl Acad Sci U S.A."},{"issue":"4","key":"2024020318491971000_jbmr2242-bib-0017","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1074\/jbc.M207872200","article-title":"Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production","volume":"278","author":"Saito","year":"2003","journal-title":"J Biol Chem."},{"issue":"8","key":"2024020318491971000_jbmr2242-bib-0018","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1210\/endo.143.8.8795","article-title":"Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo","volume":"143","author":"Shimada","year":"2002","journal-title":"Endocrinology."},{"issue":"9","key":"2024020318491971000_jbmr2242-bib-0019","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1172\/JCI31330","article-title":"A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis","volume":"117","author":"Ichikawa","year":"2007","journal-title":"J Clin Invest."},{"issue":"10","key":"2024020318491971000_jbmr2242-bib-0020","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1074\/jbc.C500457200","article-title":"Regulation of fibroblast growth factor-23 signaling by klotho","volume":"281","author":"Kurosu","year":"2006","journal-title":"J Biol Chem."},{"issue":"7120","key":"2024020318491971000_jbmr2242-bib-0021","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/nature05315","article-title":"Klotho converts canonical FGF receptor into a specific receptor for FGF23","volume":"444","author":"Urakawa","year":"2006","journal-title":"Nature."},{"issue":"4","key":"2024020318491971000_jbmr2242-bib-0022","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1210\/jc.2004-2302","article-title":"A novel GALNT3 mutation in a pseudoautosomal dominant form of tumoral calcinosis: evidence that the disorder is autosomal recessive","volume":"90","author":"Ichikawa","year":"2005","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2024020318491971000_jbmr2242-bib-0023","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/ng1358","article-title":"Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis","volume":"36","author":"Topaz","year":"2004","journal-title":"Nat Genet."},{"issue":"2","key":"2024020318491971000_jbmr2242-bib-0024","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1359\/jbmr.061105","article-title":"Hyperostosis-hyperphosphatemia syndrome: a congenital disorder of O-glycosylation associated with augmented processing of fibroblast growth factor 23","volume":"22","author":"Frishberg","year":"2007","journal-title":"J Bone Miner Res."},{"issue":"27","key":"2024020318491971000_jbmr2242-bib-0025","doi-asserted-by":"crossref","first-page":"18370","DOI":"10.1074\/jbc.M602469200","article-title":"Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation","volume":"281","author":"Kato","year":"2006","journal-title":"J Biol Chem."},{"issue":"3","key":"2024020318491971000_jbmr2242-bib-0026","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1359\/JBMR.0301264","article-title":"FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis","volume":"19","author":"Shimada","year":"2004","journal-title":"J Bone Miner Res."},{"issue":"7","key":"2024020318491971000_jbmr2242-bib-0027","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1210\/en.2003-1768","article-title":"Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis","volume":"145","author":"Larsson","year":"2004","journal-title":"Endocrinology."},{"issue":"11","key":"2024020318491971000_jbmr2242-bib-0028","doi-asserted-by":"crossref","first-page":"5269","DOI":"10.1210\/en.2004-0233","article-title":"Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders","volume":"145","author":"Bai","year":"2004","journal-title":"Endocrinology."},{"issue":"5","key":"2024020318491971000_jbmr2242-bib-0029","doi-asserted-by":"crossref","first-page":"F1088","DOI":"10.1152\/ajprenal.00474.2004","article-title":"Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism","volume":"289","author":"Shimada","year":"2005","journal-title":"Am J Physiol Renal Physiol."},{"issue":"5","key":"2024020318491971000_jbmr2242-bib-0030","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1210\/jc.2006-1825","article-title":"Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations","volume":"92","author":"Ichikawa","year":"2007","journal-title":"J Clin Endocrinol Metab."},{"issue":"11","key":"2024020318491971000_jbmr2242-bib-0031","doi-asserted-by":"crossref","first-page":"4472","DOI":"10.1210\/jc.2006-1247","article-title":"Tumoral calcinosis presenting with eyelid calcifications due to novel missense mutations in the glycosyl transferase domain of the GALNT3 gene","volume":"91","author":"Ichikawa","year":"2006","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2024020318491971000_jbmr2242-bib-0032","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1210\/en.2008-0877","article-title":"Ablation of the Galnt3 gene leads to low-circulating intact fibroblast growth factor 23 (Fgf23) concentrations and hyperphosphatemia despite increased Fgf23 expression","volume":"150","author":"Ichikawa","year":"2009","journal-title":"Endocrinology."},{"issue":"12","key":"2024020318491971000_jbmr2242-bib-0033","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1210\/en.2011-1137","article-title":"Dietary phosphate restriction normalizes biochemical and skeletal abnormalities in a murine model of tumoral calcinosis","volume":"152","author":"Ichikawa","year":"2011","journal-title":"Endocrinology."},{"issue":"3","key":"2024020318491971000_jbmr2242-bib-0034","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1079\/BJN20061838","article-title":"High phosphorus intakes acutely and negatively affect Ca and bone metabolism in a dose-dependent manner in healthy young females","volume":"96","author":"Kemi","year":"2006","journal-title":"Br J Nutr."},{"issue":"10","key":"2024020318491971000_jbmr2242-bib-0035","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1017\/S1368980009004819","article-title":"Habitual high phosphorus intakes and foods with phosphate additives negatively affect serum parathyroid hormone concentration: a cross-sectional study on healthy premenopausal women","volume":"12","author":"Kemi","year":"2009","journal-title":"Public Health Nutr."},{"issue":"8","key":"2024020318491971000_jbmr2242-bib-0036","doi-asserted-by":"crossref","first-page":"e43205","DOI":"10.1371\/journal.pone.0043205","article-title":"A mouse with an N-Ethyl-N-nitrosourea (ENU) Induced Trp589Arg Galnt3 mutation represents a model for hyperphosphataemic familial tumoural calcinosis","volume":"7","author":"Esapa","year":"2012","journal-title":"PLoS One."},{"issue":"8","key":"2024020318491971000_jbmr2242-bib-0037","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1097\/00000478-199308000-00004","article-title":"Familial tumoral calcinosis. A clinical, histopathologic, and ultrastructural study with an analysis of its calcifying process and pathogenesis","volume":"17","author":"Slavin","year":"1993","journal-title":"Am J Surg Pathol."},{"issue":"2","key":"2024020318491971000_jbmr2242-bib-0038","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.bone.2012.10.030","article-title":"Occurrence of new bone-like tissue formation in uremic tumoral calcinosis","volume":"52","author":"Hiramatsu","year":"2013","journal-title":"Bone."},{"issue":"7","key":"2024020318491971000_jbmr2242-bib-0039","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1007\/s00198-011-1838-0","article-title":"FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages","volume":"23","author":"Desjardins","year":"2012","journal-title":"Osteoporos Int."},{"issue":"6","key":"2024020318491971000_jbmr2242-bib-0040","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s00467-011-1822-0","article-title":"Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients","volume":"26","author":"Srivaths","year":"2011","journal-title":"Pediatr Nephrol."},{"issue":"20","key":"2024020318491971000_jbmr2242-bib-0041","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1056\/NEJM200005183422003","article-title":"Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis","volume":"342","author":"Goodman","year":"2000","journal-title":"N Engl J Med."},{"issue":"11","key":"2024020318491971000_jbmr2242-bib-0042","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1681\/ASN.2006121397","article-title":"Mineral metabolism and vascular damage in children on dialysis","volume":"18","author":"Shroff","year":"2007","journal-title":"J Am Soc Nephrol."},{"issue":"2","key":"2024020318491971000_jbmr2242-bib-0043","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.atherosclerosis.2010.09.020","article-title":"Cardiac and arterial calcifications and all-cause mortality in the elderly: the PROTEGER Study","volume":"213","author":"Zhang","year":"2010","journal-title":"Atherosclerosis."},{"issue":"10","key":"2024020318491971000_jbmr2242-bib-0044","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1681\/ASN.2010121224","article-title":"FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis","volume":"22","author":"Kendrick","year":"2011","journal-title":"J Am Soc Nephrol."},{"issue":"12","key":"2024020318491971000_jbmr2242-bib-0045","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1093\/ndt\/gfq309","article-title":"FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment","volume":"25","author":"Seiler","year":"2010","journal-title":"Nephrol Dial Transplant."},{"issue":"11","key":"2024020318491971000_jbmr2242-bib-0046","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1172\/JCI46122","article-title":"FGF23 induces left ventricular hypertrophy","volume":"121","author":"Faul","year":"2011","journal-title":"J Clin Invest."},{"issue":"2","key":"2024020318491971000_jbmr2242-bib-0047","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/jbmr.544","article-title":"A Phex mutation in a murine model of X-linked hypophosphatemia alters phosphate responsiveness of bone cells","volume":"27","author":"Ichikawa","year":"2012","journal-title":"J Bone Miner Res."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.2242","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/29\/9\/2017\/56565613\/jbmr2242.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/29\/9\/2017\/56565613\/jbmr2242.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:52:00Z","timestamp":1710341520000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/29\/9\/2017-2023\/7598925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,1]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2014,4,1]]},"published-print":{"date-parts":[[2014,9,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.2242","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,9,1]]},"published":{"date-parts":[[2014,4,1]]}}}