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Publication : Mouse vitamin D-24-hydroxylase: molecular cloning, tissue distribution, and transcriptional regulation by 1alpha,25-dihydroxyvitamin D3.

First Author  Akeno N Year  1997
Journal  Endocrinology Volume  138
Issue  6 Pages  2233-40
PubMed ID  9165006 Mgi Jnum  J:41002
Mgi Id  MGI:892721 Doi  10.1210/endo.138.6.5170
Citation  Akeno N, et al. (1997) Mouse vitamin D-24-hydroxylase: molecular cloning, tissue distribution, and transcriptional regulation by 1alpha,25-dihydroxyvitamin D3. Endocrinology 138(6):2233-40
abstractText  Vitamin D-24-hydroxylase (24-OHase) is a cytochrome P-450 enzyme that catalyzes the conversion of 25-hydroxyvitamin D3 (25OHD3) and 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] to 24,25-dihydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3, respectively. A full-length complementary DNA for mouse 24-OHase has now been characterized. The complementary DNA consists of 3309 bp and encodes a protein of 514 amino acids that shows 82% and 95% sequence identity with the human and rat enzymes, respectively. Northern blot analysis of tissues from mice injected with 1,25-(OH)2D3 (24 pmol/g) revealed that the 3.4-kb 24-OHase messenger RNA (mRNA) is most abundant in kidney and intestine, with smaller amounts present in skin, thymus, and bone. RT-PCR and Southern blot analysis detected 24-OHase mRNA in several other tissues including lung, testis, spleen, pancreas, and heart. Intraperitoneal injection of 1,25-(OH)2D3 induced dose- and time-dependent increases in both 24-OHase mRNA abundance and enzyme activity in mouse kidney. Similarly, 1,25-(OH)2D3-induced increases in both 24-OHase mRNA and activity were apparent in the duodenum. Although 1,25-(OH)2D3 increased the amount of 24-OHase mRNA in skin, enzyme activity was not detected in this tissue. Pretreatment of mice with cycloheximide (400 microg/g), an inhibitor of protein synthesis, potentiated the increase in 24-OHase mRNA abundance, but blocked the increase in 24-OHase activity, induced by 1,25-(OH)2D3 in kidney and duodenum, suggesting that 24-OHase gene expression may be regulated not only by the vitamin D receptor but also by a short-lived repressor protein.
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