ArticleThe Journal of pathology2008
Amelioration of the premature ageing-like features of Fgf-23 knockout mice by genetically restoring the systemic actions of FGF-23.
Article in The Journal of pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 68 citations in OpenAlex.
- Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2017Trial
- Review
- The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026Review
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- The FGF13-Caveolin-1 Axis: A Key Player in the Pathogenesis of Doxorubicin- and D-Galactose-Induced Premature Cardiac Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Elevated phosphate levels in CKD - a direct threat for the heart.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Article
- The vitamin DAmerican journal of physiology. Cell physiology · 2025Article
- Non-Classical Effects of FGF23: Molecular and Clinical Features.International journal of molecular sciences · 2024Review
- Determination of the reference interval for urinary klotho to creatinine ratio of healthy dogs.Frontiers in veterinary science · 2024Article
- The impact of SGLT2 inhibitors on αKlotho in renal MDCK and HK-2 cells.Frontiers in endocrinology · 2023Article
- Interactions between FGF23 and vitamin D.Endocrine connections · 2022Review
- Salivary phosphate as a biomarker for human diseases.FASEB bioAdvances · 2022Article
- Phosphate Dysregulation and Neurocognitive Sequelae.Advances in experimental medicine and biology · 2022Article
- A Land of Controversy: Fibroblast Growth Factor-23 and Uremic Cardiac Hypertrophy.Journal of the American Society of Nephrology : JASN · 2020Review
- Renal involvement in the pathogenesis of mineral and bone disorder in dystrophin-deficient mdx mouse.The journal of physiological sciences : JPS · 2019Article
- Dietary phosphate toxicity: an emerging global health concern.Histochemistry and cell biology · 2018Review
- Interrelated role of Klotho and calcium-sensing receptor in parathyroid hormone synthesis and parathyroid hyperplasia.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease.Scientific reports · 2017Article
- Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity.BoneKEy reports · 2015Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
Genetic ablation of fibroblast growth factor 23 from mice (Fgf-23(-/-)) results in a short lifespan with numerous abnormal biochemical and morphological features. Such features include kyphosis, hypogonadism and associated infertility, osteopenia, pulmonary emphysema, severe vascular and soft tissue calcifications, and generalized atrophy of various tissues. To determine whether these widespread anomalies in Fgf-23(-/-) mice can be ameliorated by genetically restoring the systemic actions of FGF-23, we generated Fgf-23(-/-) mice expressing the human FGF-23 transgene in osteoblasts under the control of the 2.3 kb alpha1(I) collagen promoter (Fgf-23(-/-) /hFGF-23-Tg double mutants). This novel mouse model is completely void of all endogenous Fgf-23 activity, but produces human FGF-23 in bone cells that is subsequently released into the circulation. Our results suggest that lack of Fgf-23 activities results in extensive premature ageing-like features and early mortality of Fgf-23(-/-) mice, while restoring the systemic effects of FGF-23 significantly ameliorates these phenotypes, with the resultant effect being improved growth, restored fertility, and significantly prolonged survival of double mutants. With regard to their serum biochemistry, double mutants reversed the severe hyperphosphataemia, hypercalcaemia, and hypervitaminosis D found in Fgf-23(-/-) littermates; rather, double mutants show hypophosphataemia and normal serum 1,25-dihydroxyvitamin D(3) levels similar to pure FGF-23 Tg mice. These changes were associated with reduced renal expression of NaPi2a and 1 alpha-hydroxylase, compared to Fgf-23(-/-) mice. FGF-23 acts to prevent widespread abnormal features by acting systemically to regulate phosphate homeostasis and vitamin D metabolism. This novel mouse model provides us with an in vivo tool to study the systemic effects of FGF-23 in regulating mineral ion metabolism and preventing multiple abnormal phenotypes without the interference of native Fgf-23.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.