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To more finely test the role of systemic and genetic influences in FGF23 production, a mouse was developed that carried a floxed (\u201cf\u201d)-Fgf23 allele (exon 2 floxed) which demonstrated in vivo recombination when bred to global-Cre transgenic mice (eIIa-cre). Mice homozygous for the recombined allele (\u201c\u0394\u201d) had undetectable serum intact FGF23, elevated serum phosphate (p\u2009&amp;lt;\u20090.05), and increased kidney Cyp27b1 mRNA (p\u2009&amp;lt;\u20090.05), similar to global Fgf23-KO mice. To isolate cellular FGF23 responses during phosphate challenge, Fgf23\u0394\/f mice were mated with early osteoblast type I\u03b11 collagen 2.3-kb promoter-cre mice (Col2.3-cre) and the late osteoblast\/early osteocyte Dentin matrix protein-1-cre (Dmp1-cre). Fgf23\u0394\/f\/Col2.3-cre+ and Fgf23\u0394\/f\/Dmp1-cre+ exhibited reduced baseline serum intact FGF23 versus controls. After challenge with high-phosphate diet Cre\u2013 mice had 2.1-fold to 2.5-fold increased serum FGF23 (p\u2009&amp;lt;\u20090.01), but Col2.3-cre+ mice had no significant increase, and Dmp1-cre+ mice had only a 37% increase (p\u2009&amp;lt;\u20090.01) despite prevailing hyperphosphatemia in both models. The Fgf23\u0394\/f\/Col2.3-cre was bred onto the Hyp (murine X-linked hypophosphatemia [XLH] model) genetic background to test the contribution of osteoblasts and osteocytes to elevated FGF23 and Hyp disease phenotypes. Whereas Hyp mice maintained inappropriately elevated FGF23 considering their marked hypophosphatemia, Hyp\/Fgf23\u0394\/f\/Col2.3-cre+ mice had serum FGF23 &amp;lt;4% of Hyp (p\u2009&amp;lt;\u20090.01), and this targeted restriction normalized serum phosphorus and ricketic bone disease. In summary, deleting FGF23 within early osteoblasts and osteocytes demonstrated that both cell types contribute to baseline circulating FGF23 concentrations, and that targeting osteoblasts\/osteocytes for FGF23 production can modify systemic responses to changes in serum phosphate concentrations and rescue the Hyp genetic syndrome. \u00a9 2016 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.2792","type":"journal-article","created":{"date-parts":[[2016,1,21]],"date-time":"2016-01-21T08:35:16Z","timestamp":1453365316000},"page":"1247-1257","source":"Crossref","is-referenced-by-count":71,"title":["Conditional Deletion of Murine\n                    <i>Fgf23<\/i>\n                    : Interruption of the Normal Skeletal Responses to Phosphate Challenge and Rescue of Genetic Hypophosphatemia"],"prefix":"10.1093","volume":"31","author":[{"given":"Erica L","family":"Clinkenbeard","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn A","family":"Cass","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M","family":"Hum","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresita","family":"Bellido","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E","family":"White","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,1,21]]},"reference":[{"key":"2024021014182954800_jbmr2792-bib-0001","first-page":"5039","volume-title":"The metabolic and molecular bases of inherited 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