Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b⁺/⁻ mice

Am J Physiol Renal Physiol. 2011 Nov;301(5):F1105-13. doi: 10.1152/ajprenal.00663.2010. Epub 2011 Aug 3.


An inorganic phosphate (P(i))-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent P(i) (Na/P(i)) transport system is involved in intestinal P(i) absorption and is regulated by several factors. The type II sodium-dependent P(i) transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports P(i). In the present study, we analyzed the phenotype of Npt2b(-/-) and hetero(+/-) mice. Npt2b(-/-) mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b(+/-) mice showed hypophosphatemia and low urinary P(i) excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)(2)D(3) levels were significantly increased in Npt2b(+/-) mice compared with Npt2b(+/+) mice. Npt2b mRNA levels were reduced to 50% that in Npt2b(+/+) mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b(+/-) mice. At 20 wk of age, Npt2b(+/-) mice showed hypophosphaturia and reduced Na/P(i) cotransport activity in the distal intestine. Npt2b(+/+) mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b(+/-) mice treated with adenine had significantly reduced plasma P(i) levels compared with Npt2b(+/+) mice. Intestinal Npt2b protein and Na(+)/P(i) transport activity levels were significantly lower in Npt2b(+/-) mice than in the Npt2b(+/+) mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia.

MeSH terms

  • Adenine
  • Animals
  • Blotting, Western
  • Body Weight / physiology
  • Chromosomes, Artificial, Bacterial / genetics
  • DNA / genetics
  • Diet
  • Female
  • Genetic Vectors
  • Genotype
  • Homeostasis / physiology*
  • Intestinal Mucosa / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microvilli / metabolism
  • Phosphates / blood
  • Phosphates / metabolism*
  • Polymerase Chain Reaction
  • Pregnancy
  • Renal Insufficiency / chemically induced
  • Renal Insufficiency / metabolism
  • Sodium / metabolism
  • Sodium-Phosphate Cotransporter Proteins, Type IIb / genetics*
  • Sodium-Phosphate Cotransporter Proteins, Type IIb / physiology*


  • Phosphates
  • Slc34a2 protein, mouse
  • Sodium-Phosphate Cotransporter Proteins, Type IIb
  • DNA
  • Sodium
  • Adenine