Journal
KIDNEY INTERNATIONAL
Volume 75, Issue 11, Pages 1166-1172Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2009.24
Keywords
FGF23; phosphate; PTH
Categories
Funding
- NIAMS NIH HHS [R01 AR050560-03, R01 AR050560] Funding Source: Medline
- NIDDK NIH HHS [R01-DK077276, R01 DK073944-02, R01 DK073944, R01 DK077276, R01 DK077276-02] Funding Source: Medline
Ask authors/readers for more resources
Changes in the expression of klotho, a beta-glucuronidase, contribute to the development of features that resemble those of premature aging, as well as chronic renal failure. Klotho knockout mice have increased expression of the sodium/phosphate cotransporter (NaPi2a) and 1 alpha-hydroxylase in their kidneys, along with increased serum levels of phosphate and 1,25-dihydroxyvitamin D. These changes are associated with widespread soft-tissue calcifications, generalized tissue atrophy, and a shorter lifespan in the knockout mice. To determine the role of the increased vitamin D activities in klotho knockout animals, we generated klotho and 1 alpha-hydroxylase double-knockout mice. These double mutants regained body weight and developed hypophosphatemia with a complete elimination of the soft-tissue and vascular calcifications that were routinely found in klotho knockout mice. The markedly increased serum fibroblast growth factor 23 and the abnormally low serum parathyroid hormone levels, typical of klotho knockout mice, were significantly reversed in the double-knockout animals. These in vivo studies suggest that vitamin D has a pathologic role in regulating abnormal mineral ion metabolism and soft-tissue anomalies of klotho-deficient mice. Kidney International (2009) 75, 1166-1172; doi:10.1038/ki.2009.24; published online 18 February 2009
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available