{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:09:12Z","timestamp":1787508552807,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,7,14]],"date-time":"2008-07-14T00:00:00Z","timestamp":1215993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Genetic ablation of fibroblast growth factor 23 from mice (\n                    <jats:italic>Fgf\u201023<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) results in a short lifespan with numerous abnormal biochemical and morphological features. Such features include kyphosis, hypogonadism and associated infertility, osteopenia, pulmonary emphysema, severe vascular and soft tissue calcifications, and generalized atrophy of various tissues. To determine whether these widespread anomalies in\n                    <jats:italic>Fgf\u201023<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice can be ameliorated by genetically restoring the systemic actions of FGF\u201023, we generated\n                    <jats:italic>Fgf\u201023<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice expressing the human\n                    <jats:italic>FGF\u201023<\/jats:italic>\n                    transgene in osteoblasts under the control of the 2.3 kb \u03b11(I) collagen promoter (\n                    <jats:italic>Fgf\u201023<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <jats:italic>\/hFGF\u201023\u2010Tg<\/jats:italic>\n                    double mutants). This novel mouse model is completely void of all endogenous Fgf\u201023 activity, but produces human FGF\u201023 in bone cells that is subsequently released into the circulation. Our results suggest that lack of\n                    <jats:italic>Fgf\u201023<\/jats:italic>\n                    activities results in extensive premature ageing\u2010like features and early mortality of\n                    <jats:italic>Fgf\u201023<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, while restoring the systemic effects of FGF\u201023 significantly ameliorates these phenotypes, with the resultant effect being improved growth, restored fertility, and significantly prolonged survival of double mutants. With regard to their serum biochemistry, double mutants reversed the severe hyperphosphataemia, hypercalcaemia, and hypervitaminosis D found in\n                    <jats:italic>Fgf\u201023<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    littermates; rather, double mutants show hypophosphataemia and normal serum 1,25\u2010dihydroxyvitamin D\n                    <jats:sub>3<\/jats:sub>\n                    levels similar to pure\n                    <jats:italic>FGF\u201023 Tg<\/jats:italic>\n                    mice. These changes were associated with reduced renal expression of NaPi2a and 1\u03b1\u2010hydroxylase, compared to\n                    <jats:italic>Fgf\u201023<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. FGF\u201023 acts to prevent widespread abnormal features by acting systemically to regulate phosphate homeostasis and vitamin D metabolism. This novel mouse model provides us with an\n                    <jats:italic>in vivo<\/jats:italic>\n                    tool to study the systemic effects of FGF\u201023 in regulating mineral ion metabolism and preventing multiple abnormal phenotypes without the interference of native Fgf\u201023. Copyright \u00a9 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2409","type":"journal-article","created":{"date-parts":[[2008,7,14]],"date-time":"2008-07-14T10:26:30Z","timestamp":1216031190000},"page":"345-355","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Amelioration of the premature ageing\u2010like features of\n                    <i>Fgf\u201023<\/i>\n                    knockout mice by genetically restoring the systemic actions of 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