Analysis of vitamin D-dependent calcium-binding protein messenger ribonucleic acid expression in mice lacking the...

To investigate the roles of the receptor-dependent actions of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in the regulation of vitamin D-dependent calcium-binding proteins (calbindin-D), the messenger RNA (mRNA) levels of calbindin-D9k and -28k were examined in vitamin D receptor (VDR)-ablated mice and control littermates. In VDR-ablated mice, calbindin-D9k mRNA was dramatically reduced in the intestine, kidneys, lungs, and brain; however, calbindin-D28k mRNA was only moderately decreased in the kidney. After 1,25-(OH)2D3 injection, calbindin-D9k mRNA levels and renal and alveolar calbindin-D28k mRNA levels were induced in control animals, but not in the homozygous mice. When the mice were fed a diet high in lactose, calcium, and phosphorus, intestinal calbindin-D9k mRNA levels in the homozygous mice were restored to those in their control littermates. However, this diet failed to normalize extraintestinal calbindin mRNA levels. These findings demonstrate that the receptor-dependent actions of 1,25-(OH)2D3 regulate calbindin-D9k gene expression and that tissue-specific factors modulate the effects of 1,25-(OH)2D3 on calbindin-D28k gene expression. These data also demonstrate that in the absence of a functional VDR, a high local concentration of calcium, phosphorus, and/or lactose in the intestinal lumen can normalize intestinal calbindin-D9k mRNA levels.