{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:35:37Z","timestamp":1791178537628,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,5,9]],"date-time":"2012-05-09T00:00:00Z","timestamp":1336521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>X\u2010linked hypophosphatemic rickets (XLH) is a dominantly inherited disease characterized by renal phosphate wasting, aberrant vitamin D metabolism, and defective bone mineralization. It is known that XLH in humans and in certain mouse models is caused by inactivating mutations in <jats:italic>PHEX\/Phex<\/jats:italic> (phosphate\u2010regulating gene with homologies to endopeptidases on the X chromosome). By a genome\u2010wide <jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (ENU)\u2010induced mutagenesis screen in mice, we identified a dominant mouse mutation that exhibits the classic clinical manifestations of XLH, including growth retardation, skeletal abnormalities (rickets\/osteomalacia), hypophosphatemia, and increased serum alkaline phosphatase (ALP) levels. Mapping and sequencing revealed that these mice carry a point mutation in exon 14 of the Phex gene that introduces a stop codon at amino acid 496 of the coding sequence (<jats:italic>Phex<\/jats:italic><jats:sup><jats:italic>Jrt<\/jats:italic><\/jats:sup> also published as <jats:italic>Phex<\/jats:italic><jats:sup>K496X<\/jats:sup> [Ichikawa et al., <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#bib19\">2012<\/jats:ext-link>]). Fgf23 mRNA expression as well as that of osteocalcin, bone sialoprotein, and matrix extracellular phosphoglycoprotein was upregulated in male mutant long bone, but that of sclerostin was unaffected. Although Phex mRNA is expressed in bone from mutant hemizygous male mice (<jats:italic>Phex<\/jats:italic><jats:sup><jats:italic>Jrt<\/jats:italic><\/jats:sup>\/Y mice), no Phex protein was detected in immunoblots of femoral bone protein. Stromal cultures from mutant bone marrow were indistinguishable from those of wild\u2010type mice with respect to differentiation and mineralization. The ability of <jats:italic>Phex<\/jats:italic><jats:sup><jats:italic>Jrt<\/jats:italic><\/jats:sup>\/Y osteoblasts to mineralize and the altered expression levels of matrix proteins compared with the well\u2010studied <jats:italic>Hyp<\/jats:italic> mice makes it a unique model with which to further explore the clinical manifestations of XLH and its link to FGF23 as well as to evaluate potential new therapeutic strategies. J. Cell. Biochem. 113: 2432\u20132441, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24115","type":"journal-article","created":{"date-parts":[[2012,3,5]],"date-time":"2012-03-05T15:12:26Z","timestamp":1330960346000},"page":"2432-2441","source":"Crossref","is-referenced-by-count":19,"title":["A novel <i>Phex<\/i> mutation in a new mouse model of hypophosphatemic rickets"],"prefix":"10.1002","volume":"113","author":[{"given":"Celeste","family":"Owen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frieda","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Flenniken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy R.","family":"Osborne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Ichikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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