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Analysis of Vitamin D-Dependent Calcium-Binding Protein Messenger Ribonucleic Acid Expression in Mice Lacking the Vitamin D Receptor¹

Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Marie B. Demay, M.D., Endocrine Unit, Wellman 501, Massachusetts General Hospital, 32 Fruit Street, Boston, Massachusetts 02114.

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.

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