The Tmprss6(-/-) Mouse Model Of Iron Refractory Iron Deficiency Anemia ( Irida) Exhibits Disrupted Phosphate Homeostasis, Elevated Circulating Fgf23 Levels, And Increased Fgf23 Expression In Bone Marrow

While the effects of chronic iron deficiency on erythropoiesis are well documented, the effects of iron deficiency on metabolism remain poorly understood. Recent studies suggest that iron deficiency anemia may impact systemic phosphate regulation (Farrow et al ., PNAS, 2011; Clinkenbeard et al ., J Bone Miner Res, 2014; David et al ., Kidney Int, 2016; Hanudel et al ., Am J Physiol Renal Physiol, 2016). Here we used Tmprss6-/- mice, a model of iron refractory iron deficiency anemia (IRIDA) characterized by hepcidin elevation, to explore the relationship between systemic iron deficiency and phosphate homeostasis. By intercrossing Tmprss6+/- mice, we generated Tmprss6-/- mice and littermate controls, which were raised on a standard rodent diet (Teklad 2018S containing 200 ppm iron and 0.7% phosphorus) prior to study at 8 weeks of age. Tmprss6-/- mice displayed a trend toward lower serum phosphate concentration, as well as a significant elevation in the urinary phosphate/creatinine ratio. Because of the role of phosphate in bone mineralization, we also analyzed the tibiae of Tmprss6-/- mice and found that they showed alterations in bone histology and biomechanical properties.