NDT Advance Access published online on October 2, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm672
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Gene Expression Analysis of Kidneys From Transgenic Mice Expressing Fibroblast Growth Factor-23
1 Department of Surgical Sciences 2 Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden 3 Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Gothenburg University, Gothenburg, Sweden
Correspondence and offprint requests to: Correspondence and offprint requests to: Richard Marsell, Department of Surgical Sciences, Uppsala University Hospital, Uppsala 751 85, Sweden. Fax: +46-18-50-09-52; E-mail: Richard.Marsell{at}surgsci.uu.se
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Abstract |
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Background. Fibroblast growth factor-23 (FGF23), a circulating protein produced in bone, causes decreased renal inorganic phosphate (Pi) reabsorption by reducing the expression of the sodium phosphate cotransporter type 2a (Npt2a). We have previously generated transgenic mice expressing human wild-type (WT) FGF23 under the control of the 
1 (I) collagen promoter.
Methods. In this study, we performed a large-scale gene expression study of kidneys from FGF23 transgenic mice and WT littermates. Microarray expression data of key transcripts were verified by real-time RT-PCR analysis.
Results. Several genes that play a role in Pi regulation revealed decreased expression levels in the transgenic mice, such as Npt2a and Pdzk1, a scaffolding protein known to interact with Npt2a. Importantly, Klotho, a suggested FGF23 receptor cofactor, was the most significantly decreased transcript and 2-Na+/K+-ATPase (Atp1a2), a gene isoform of 1-Na+/K+-ATPase (Atp1a1) which has recently been shown to interact with Klotho and regulate calcium metabolism, was the most increased transcript. In contrast, other genes proposed to regulate Pi levels, such as secreted frizzled-related protein-4 (sFrp4) and Na+/H+ exchanger regulatory factor-1 (Nherf1) revealed no changes.
Conclusions. FGF23 transgenic mice display differentially expressed transcript levels of several genes essential in renal Pi regulation. These findings may lead to further understanding of how FGF23 mediates its actions on renal Pi regulation.
Keywords: Atp1a1; Atp1a2; FGF-23; Klotho; phosphate
Received for publication: 13. 7.07
Accepted in revised form: 3. 9.07
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