High dietary phosphate intake induces development of ectopic calcifications in a murine model of familial tumoral calcinosis

Shoji Ichikawa, Amie K. Gray, Leah R. Padgett, Austin M. Reilly, Tyler R. Unsicker

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Familial tumoral calcinosis is characterized by ectopic calcifications due to persistent hyperphosphatemia. The most common genetic cause of the disease is mutations in GALNT3, encoding a glycosyltransferase involved in a posttranslational modification of fibroblast growth factor 23 (FGF23). The Galnt3 knockout mouse we developed was hyperphosphatemic due to low intact Fgf23 levels, but did not develop any apparent calcifications on a standard rodent diet. We therefore tested the hypothesis that a further challenge with a high phosphate diet could induce ectopic calcifications in Galnt3 knockout mice. Mice were fed either normal (0.6%) or high (1.65%) phosphate diet for 20 weeks beginning from weaning at 3 weeks. The high phosphate diet did not affect serum phosphorus concentration. However, regardless of the dietary phosphate contents, serum phosphorus levels were consistently elevated in Galnt3 knockout mice. The mice on the high phosphate diet had slightly low serum calcium, but significantly high alkaline phosphatase, parathyroid hormone (PTH), and calcium in the kidney. Although none of Galnt3 knockout mice on the normal phosphate diet developed calcifications, calcifications appeared in approximately one-half of the mice on the high phosphate diet by 12 weeks. Calcified masses were most often found around the neck and on the back and as large as 9.9mm in length. These data indicate that dietary phosphate load has major impact on the development of ectopic calcifications in tumoral calcinosis.

Original languageEnglish (US)
Pages (from-to)2017-2023
Number of pages7
JournalJournal of Bone and Mineral Research
Volume29
Issue number9
DOIs
StatePublished - Sep 2014

Keywords

  • ECTOPIC CALCIFICATION
  • FGF23
  • GALNT3 KNOCKOUT MICE
  • HYPERPHOSPHATEMIA
  • TUMORAL CALCINOSIS

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

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