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Updated: Mar 19, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
FGF23 Neutralizing Antibody Ameliorates Hypophosphatemia and Impaired FGF Receptor Signaling in Kidneys of HMWFGF2
E Du1, L Xiao1, M M Hurley1
1Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut.
Abstract:
High molecular weight FGF2 transgenic mice (HMWTg) phenocopy the Hyp mouse, homolog of human X-linked hypophosphatemic rickets with phosphate wasting and abnormal fibroblast growth factor (FGF23), fibroblast growth factor receptor (FGFR), Klotho and mitogen activated protein kinases (MAPK) signaling in kidney. In this study, we assessed whether short-term (24 h) in vivo administration of FGF23 neutralizing antibody (FGF23Ab) could rescue hypophosphatemia and impaired FGFR signaling in kidneys of HMWTg male mice. Bone mineral density and bone mineral content in 1-month-old HMWTg mice were significantly reduced compared with Control/VectorTg mice. Serum FGF23 was significantly increased in HMWTg compared with VectorTg. Serum phosphate was significantly reduced in HMWTg and was rescued by FGF23Ab. Serum parathyroid hormone (PTH) was significantly increased in HMWTg but was not reduced by FGF23Ab. 1, 25(OH)2 D was inappropriately normal in serum of HMWTg and was significantly increased in both Vector and HMWTg by FGF23Ab. Analysis of HMWTg kidneys revealed significantly increased mRNA expression of the FGF23 co-receptor Klotho, transcription factor mRNAs for early growth response-1 transcription factor (Egr-1), and c-fos were all significantly decreased by FGF23Ab. A significant reduction in the phosphate transporter Npt2a mRNA was also observed in HMWTg kidneys, which was increased by FGF23Ab. FGF23Ab reduced p-FGFR1, p-FGFR3, KLOTHO, p-ERK1/2, C-FOS, and increased NPT2A protein in HMWTg kidneys. We conclude that FGF23 blockade rescued hypophosphatemia by regulating FGF23/FGFR downstream signaling in HMWTg kidneys. Furthermore, HMWFGF2 isoforms regulate PTH expression independent of FGF23/FGFR signaling. J. Cell. Physiol. 232: 610-616, 2017. © 2016 Wiley Periodicals, Inc.
Insights
High molecular weight FGF2 transgenic mice experienced hypophosphatemia, which was rescued by FGF23 neutralizing antibody treatment. This FGF23 blockade improved FGFR signaling and phosphate transport in the kidneys.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- High molecular weight FGF2 transgenic mice (HMWTg) model X-linked hypophosphatemic rickets, exhibiting phosphate wasting and altered FGF23/FGFR signaling.
- These mice show reduced bone mineral density and content, with elevated serum FGF23 and decreased serum phosphate.
Purpose of the Study:
- To investigate if short-term FGF23 neutralizing antibody (FGF23Ab) administration can reverse hypophosphatemia and impaired FGFR signaling in HMWTg mice.
Main Methods:
- Administered FGF23Ab to HMWTg mice and assessed serum phosphate, parathyroid hormone (PTH), and 1,25(OH)2D levels.
- Analyzed kidney mRNA expression of Klotho, Egr-1, c-fos, and Npt2a.
- Evaluated protein levels of FGFR1, FGFR3, Klotho, ERK1/2, C-FOS, and NPT2A.
Main Results:
- FGF23Ab rescued hypophosphatemia in HMWTg mice.
- FGF23Ab increased serum 1,25(OH)2D levels.
- FGF23Ab decreased kidney mRNA expression of Klotho, Egr-1, and c-fos, while increasing Npt2a mRNA.
- FGF23Ab reduced p-FGFR1, p-FGFR3, KLOTHO, p-ERK1/2, C-FOS, and increased NPT2A protein in HMWTg kidneys.
Conclusions:
- FGF23 blockade effectively rescues hypophosphatemia by modulating FGF23/FGFR downstream signaling in the kidneys of HMWTg mice.
- High molecular weight FGF2 isoforms influence PTH expression independently of FGF23/FGFR signaling.
