2009
DOI: 10.1096/fj.08-123992
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Abstract: Hyp mice possess a mutation that inactivates the phosphate-regulating gene, which is homologous to the endopeptidases of the X-chromosome (PHEX). The mutation is associated with severe hypophosphatemia due to excessive urinary phosphate wasting. Such urinary phosphate wasting in Hyp mice is associated with an increased serum accumulation of fibroblast growth factor (FGF) 23. We wanted to determine the biological significance of increased serum FGF23 levels and concomitant hypophosphatemia in Hyp mice and to ev… Show more

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Cited by 99 publications
(105 citation statements)
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“…Moreover, FGF23-induced hypophosphatemia in Hyp mice is reversed to hyperphosphatemia in the Hyp mice without alpha-klotho activity (Hyp/alpha-klotho double mutant mice), despite high serum FGF23 levels in double mutant mice. 3,36 In accordance with these animal studies, an inactivating mutation in the human alpha-klotho gene resulted in severe hyperphosphatemia, despite high serum FGF23 levels in a patient with tumoral calcinosis. 38 From the above-cited human and experimental studies, it is clear that alpha-klotho has an indispensable role in FGF23-mediated phosphate metabolism.…”
Section: Introductionmentioning
confidence: 64%
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“…Moreover, FGF23-induced hypophosphatemia in Hyp mice is reversed to hyperphosphatemia in the Hyp mice without alpha-klotho activity (Hyp/alpha-klotho double mutant mice), despite high serum FGF23 levels in double mutant mice. 3,36 In accordance with these animal studies, an inactivating mutation in the human alpha-klotho gene resulted in severe hyperphosphatemia, despite high serum FGF23 levels in a patient with tumoral calcinosis. 38 From the above-cited human and experimental studies, it is clear that alpha-klotho has an indispensable role in FGF23-mediated phosphate metabolism.…”
Section: Introductionmentioning
confidence: 64%
“…38 From the above-cited human and experimental studies, it is clear that alpha-klotho has an indispensable role in FGF23-mediated phosphate metabolism. 14,17,18,36,39,40 As mentioned, features of phosphate toxicity appear in various organs when there is a dysregulation of the FGF23-alpha-klotho system.…”
Section: Introductionmentioning
confidence: 96%
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“…30 There may be interactive effects between FGF23 and Klotho. 38,39,64,65 Although plasma FGF23 is not independently associated with cardiac remodeling ( Figure 6), a clear positive relation of plasma FGF23 levels with cardiac hypertrophy and fibrosis is present in moderate or severe Klotho deficiency (Figure 7), suggesting that FGF23 can still be pathogenic in conjunction with or perhaps, as a pathologic intermediate for Klotho deficiency.…”
Section: Discussionmentioning
confidence: 99%
“…Klotho-ablated (kl/kl) mice develop severe hyperphosphatemia, markedly elevated levels of FGF23, endogenous 1,25-dihydroxyvitamin D intoxication with resultant hypercalcemia, suppressed levels of PTH, and hypercalciuria. [4][5][6] The animals also manifest accelerated aging that can be prevented by a low phosphate diet or ablation of CYP27B1, which ameliorate the biochemical alterations. 7,8 These data suggest that disordered mineral metabolism contributes directly to shortened lifespan of kl/kl mice.…”
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confidence: 99%