CLONING AND CHARACTERIZATION OF THE VITAMIN-D-RECEPTOR FROM XENOPUS-LAEVIS

The Vitamin D receptor (VDR), a member of the nuclear receptor superfa mily, mediates the effects of 1,25-dihydroxyvitamin D-3 on mineral ion homeostasis. Although the mammalian and avian VDRs have been extensiv ely studied, little is known about the VDR in lower vertebrate species . To address this, we have isolated the Xenopus laevis VDR (xVDR) comp lementary DNA. Overall, the xVDR shares 79%, 73%, 73%, and 75% identit y at the amino acid level with the chicken, mouse, rat, and human VDRs , respectively. The amino acid residues and subdomains important for D NA binding, hormone binding, dimerization, and transactivation are mos tly conserved among all VDR species. The xVDR polypeptide can heterodi merize with the mouse retinoid X receptor alpha, bind to the rat osteo calcin vitamin D response element (VDRE), and induce vitamin D-depende nt transactivation in transfected mammalian cells. Northern analysis r eveals two xVDR messenger RNA species of 2.2 kb and 1.8 kb in stage 60 Xenopus tissues. In the adult, xVDR expression is detected in many ti ssues including kidney, intestine, skin, and bone. During Xenopus deve lopment, xVDR messenger RNA first appears at developmental stage 13 (p reneurulation), increasing to maximum at stages 57-61 (metamorphosis). Our data demonstrate that, in Xenopus, VDR expression is developmenta lly regulated and that the vitamin D endocrine system is highly conser ved during evolution.