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lüll Modulation of renal Ca2+ transport protein genes by dietary Ca2+ and 1,25-dihydroxyvitamin D3 in 25-hydroxyvitamin D3-1alpha-hydroxylase knockout mice Hoenderop JG; Dardenne O; Van Abel M; Van Der Kemp AW; Van Os CH; St -Arnaud R; Bindels RJFASEB J 2002[Sep]; 16 (11): 1398-406Pseudovitamin 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.|25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*genetics[MESH]|Administration, Oral[MESH]|Animals[MESH]|Calbindin 1[MESH]|Calbindins[MESH]|Calcitriol/administration & dosage/*pharmacology[MESH]|Calcium Channels/analysis[MESH]|Calcium-Binding Proteins/analysis/*biosynthesis/genetics[MESH]|Calcium-Transporting ATPases/biosynthesis/genetics[MESH]|Calcium/administration & dosage/blood/*pharmacology[MESH]|Cation Transport Proteins[MESH]|Kidney/chemistry/*metabolism[MESH]|Mice[MESH]|Mice, Knockout[MESH]|Plasma Membrane Calcium-Transporting ATPases[MESH]|RNA, Messenger/biosynthesis[MESH]|Rickets/genetics/metabolism[MESH]|S100 Calcium Binding Protein G/biosynthesis/genetics[MESH]|Sodium-Calcium Exchanger/biosynthesis/genetics[MESH]|TRPV Cation Channels[MESH]|Up-Regulation[MESH]|Vitamin D Deficiency/genetics/metabolism[MESH] |