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Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism
Takashi Shimada, … , Kazuma Tomizuka, Takeyoshi Yamashita
Takashi Shimada, … , Kazuma Tomizuka, Takeyoshi Yamashita
Published February 15, 2004
Citation Information: J Clin Invest. 2004;113(4):561-568. https://doi.org/10.1172/JCI19081.
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Article Endocrinology

Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism

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Abstract

Inorganic phosphate is essential for ECM mineralization and also as a constituent of important molecules in cellular metabolism. Investigations of several hypophosphatemic diseases indicated that a hormone-like molecule probably regulates serum phosphate concentration. FGF23 has recently been recognized as playing important pathophysiological roles in several hypophosphatemic diseases. We present here the evidence that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) by generating FGF23-null mice. Disruption of the Fgf23 gene did not result in embryonic lethality, although homozygous mice showed severe growth retardation with abnormal bone phenotype and markedly short life span. The Fgf23–/– mice displayed significantly high serum phosphate with increased renal phosphate reabsorption. They also showed an elevation in serum 1,25(OH)2D that was due to the enhanced expression of renal 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase) from 10 days of age. These phenotypes could not be explained by currently known regulators of mineral homeostasis, indicating that FGF23 is essential for normal phosphate and vitamin D metabolism.

Authors

Takashi Shimada, Makoto Kakitani, Yuji Yamazaki, Hisashi Hasegawa, Yasuhiro Takeuchi, Toshiro Fujita, Seiji Fukumoto, Kazuma Tomizuka, Takeyoshi Yamashita

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Serum parameters for experimental mice at 6 weeks of age

Serum parameters for experimental mice at 6 weeks of age


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ISSN: 0021-9738 (print), 1558-8238 (online)

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