Modulation of renal Ca2+ transport protein genes by dietary Ca2+ and 1,25-dihydroxyvitamin D3 in 25-hydroxyvitamin D3-1alpha-hydroxylase knockout mice

FASEB J. 2002 Sep;16(11):1398-406. doi: 10.1096/fj.02-0225com.


Pseudovitamin D-deficiency rickets (PDDR) is an autosomal disease characterized by hyperparathyroidism, rickets, and undetectable levels of 1,25-dihydroxyvitaminD3 (1,25(OH)2D3). Mice in which the 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-OHase) gene was inactivated presented the same clinical phenotype as patients with PDDR and were used to study renal expression of the epithelial Ca2+ channel (ECaC1), the calbindins, Na+/Ca2+ exchanger (NCX1), and Ca2+-ATPase (PMCA1b). Serum Ca2+ (1.20+/-0.05 mM) and mRNA/protein expression of ECaC1 (41+/-3%), calbindin-D28K (31+/-2%), calbindin-D9K (58+/-7%), NCX1 (10+/-2%), PMCA1b (96+/-4%) were decreased in 1alpha-OHase-/- mice compared with 1alpha-OHase+/- littermates. Feeding these mice a Ca2+-enriched diet normalized serum Ca2+ levels and expression of Ca2+ proteins except for calbindin-D9K expression. 1,25(OH)2D3 repletion resulted in increased expression of Ca2+ transport proteins and normalization of serum Ca2+ levels. Localization of Ca2+ transport proteins was clearly polarized in which ECaC1 was localized along the apical membrane, calbindin-D28K in the cytoplasm, and calbindin-D9K along the apical and basolateral membranes, resulting in a comprehensive mechanism facilitating renal transcellular Ca2+ transport. This study demonstrated that high dietary Ca2+ intake is an important regulator of the renal Ca2+ transport proteins in 1,25(OH)2D3-deficient status and thus contributes to the normalization of blood Ca2+ levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics*
  • Administration, Oral
  • Animals
  • Calbindin 1
  • Calbindins
  • Calcitriol / administration & dosage
  • Calcitriol / pharmacology*
  • Calcium / administration & dosage
  • Calcium / blood
  • Calcium / pharmacology*
  • Calcium Channels / analysis
  • Calcium-Binding Proteins / analysis
  • Calcium-Binding Proteins / biosynthesis*
  • Calcium-Binding Proteins / genetics
  • Calcium-Transporting ATPases / biosynthesis
  • Calcium-Transporting ATPases / genetics
  • Cation Transport Proteins
  • Kidney / chemistry
  • Kidney / metabolism*
  • Mice
  • Mice, Knockout
  • Plasma Membrane Calcium-Transporting ATPases
  • RNA, Messenger / biosynthesis
  • Rickets / genetics
  • Rickets / metabolism
  • S100 Calcium Binding Protein G / biosynthesis
  • S100 Calcium Binding Protein G / genetics
  • Sodium-Calcium Exchanger / biosynthesis
  • Sodium-Calcium Exchanger / genetics
  • TRPV Cation Channels
  • Up-Regulation
  • Vitamin D Deficiency / genetics
  • Vitamin D Deficiency / metabolism


  • Calb1 protein, mouse
  • Calbindin 1
  • Calbindins
  • Calcium Channels
  • Calcium-Binding Proteins
  • Cation Transport Proteins
  • RNA, Messenger
  • S100 Calcium Binding Protein G
  • S100g protein, mouse
  • Sodium-Calcium Exchanger
  • TRPV Cation Channels
  • Trpv5 protein, mouse
  • sodium-calcium exchanger 1
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Plasma Membrane Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Calcitriol
  • Calcium